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PubMed1996

Growth hormone versus placebo treatment for one year in growth hormone deficient adults: increase in exercise capacity and normalization of body composition.

OBJECTIVE: Studies with GH substitution in GH-deficient (GHD) adults lasting more than 6 months have so far been uncontrolled. End-points such as physical fitness and body composition may be subject to a considerable placebo effect which weakens the validity of open studies. We therefore tested GH (2 IU/m2 per day) versus placebo treatment for 12 months. DESIGN: Twenty-nine patients (mean age 45.5 +/- 2.0 years) with adult-onset GHD were studied in a double-blind, parallel design. Measurements of body composition by means of conventional anthropometry, bioelectrical impedance (BIA), CT scan and DEXA scan, exercise capacity, and isometric muscle strength were performed at baseline and after 12 months treatment. For body composition measurements a control group of 39 healthy, age and sex-matched subjects was included. RESULTS: Sum of skinfolds (SKF) at 4 sites decreased significantly after GH treatment. Total body fat (TBF) as assessed by DEXA and BIA was elevated at baseline but normalized after GH. TBF assessed by SKF revealed significantly higher levels compared to DEXA and BIA, although all estimates intercorrelated closely. Visceral and subcutaneous abdominal fat decreased by 25 and 17%, respectively after GH (P < 0.01) to levels no longer different from the control group. CT of the mid thigh revealed a significant reduction in fat tissue and a significant increase in muscle volume after GH treatment, both of which resulted in a normalization of the muscle: fat ratio (%) (placebo: 58:42 (baseline) vs 58:42 (12 months); GH: 66:34 (baseline) vs 72:28 (12 months) (P = 0.002); normal subjects: 67:33 (P < 0.05 when compared to 12 months placebo data)). Total body resistance and resistance relative to muscle volume decreased significantly after GH treatment suggesting over-hydration as compared to normal subjects. Exercise capacity (kJ) increased significantly after GH treatment (placebo: 54.7 +/- 9.8 (baseline) vs 51.6 +/- 8.2 (12 months); GH: 64.9 +/- 13.3 (baseline) vs 73.5 +/- 13.6 (12 months) (P < 0.05)). Isometric quadriceps strength increased after GH but no treatment effect could be detected owing to a small increase in the placebo group. Serum IGF-I levels (microgram/l) were low baseline and increased markedly after GH treatment to a level exceeding that of normal subjects (270 +/- 31 (12 months GH) vs 156 +/- 8 (normal subjects (P < 0.01)). The levels of serum electrolytes and HbA1c remained unchanged. The number of adverse effects were higher in the GH group after 3 months, but not after 6 and 12 months. CONCLUSIONS: (1) The reduction in excess visceral fat during GH substitution is pronounced and sustained; (2) beneficial effects on total body fat, muscle volume and physical fitness can be reproduced during prolonged placebo-controlled conditions; (3) uncontrolled data on muscle strength must be interpreted with caution; (4) a daily GH substitution dose of 2 IU/m2 seems too high in many adult patients.

Abdomen↗
PubMed2003

A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation.

BACKGROUND: Bupropion sustained release (bupropion SR) has been shown to increase smoking cessation success rates in the US studies. OBJECTIVE: To determine whether bupropion SR, in combination with counselling, is effective for smoking cessation in a multi-country study. METHODS: This randomized, double-blind, placebo-controlled trial enrolled 707 smokers. A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo. A total of 11 clinic visits and 10 telephone contacts were scheduled, during the course of 1 year. Seven-week and 12-month abstinence rates were the study outcomes. RESULTS: Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo. The continuous abstinence rate from weeks 4 to 7 was 46% in the bupropion SR group compared with 23% in the placebo group [odds ratio (OR) = 2.82; 95% confidence interval (CI) 1.89-4.28; P < 0.001). At month 12, the continuous abstinence rates were 21% for the bupropion SR group and 11% for the placebo group (OR = 2.19; 95% CI 1.29-3.86, P = 0.002). For most nicotine-withdrawal symptoms small changes were measured. Adverse events were higher for the bupropion SR group compared with placebo (insomnia 24% vs. 15%; dry mouth 13% vs. 5%). CONCLUSION: Bupropion SR in combination with counselling increased the abstinence rate compared with placebo, and was well tolerated.

Adult↗
PubMed1998

A novel therapy for nocturnal polyuria: a double-blind randomized trial of frusemide against placebo.

OBJECTIVE: To report a randomized, double-blind, placebo-controlled trial of an afternoon dose of the diuretic frusemide, used to establish an early evening diuresis and so diminish nocturnal voiding frequency and voided volume in elderly men presenting with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: After a 2-week placebo run-in period, 49 men aged > 50 years were randomized to receive 40 mg of frusemide or placebo, taken 6 h before their usual bedtime. Day and night-time frequency and voided volume during the run-in and treatment periods were compared between the placebo and frusemide groups. RESULTS: In the 43 men completing the study, there was a significant reduction in night-time frequency (-0.5 and 0) and percentage night-time voided volume (-18% and 0%) in those taking frusemide compared with placebo. Of patients on active treatment, seven of 19 had a reduction in night-time frequency of > or = 1, compared with only one of 20 on placebo, and 14 of 21 felt that frusemide had helped their nocturia, compared with only five of 22 on placebo. CONCLUSION: Men with LUTS whose most prominent symptom is nocturia should complete a frequency-volume chart. In those with nocturnal polyuria, 40 mg of frusemide resulted in a significant reduction in night-time frequency and percentage voided volume.

Aged↗
PubMed2002

Efficacy of desmopressin in the treatment of nocturia: a double-blind placebo-controlled study in men.

OBJECTIVE: To investigate the efficacy and safety of oral desmopressin in the treatment of nocturia in men. PATIENTS AND METHODS: Men aged >/=18 years with verified nocturia (>or=two voids/night) and nocturnal urine production greater than their maximum functional bladder capacity were recruited. A 3-week dose-titration phase established the optimum desmopressin dose (0.1, 0.2 or 0.4 mg). After a 1-week 'washout' period, patients who responded in the dose-titration period were randomized to receive the optimal dose of desmopressin or placebo in a double-blind design for 3 weeks. RESULTS: In all, 151 patients entered the double-blind period (86 treated with desmopressin, 65 with placebo). In the desmopressin group 28 (34%) patients and in the placebo group two (3%) patients (P<0.001) had fewer than half the number of nocturnal voids relative to baseline; the mean number of nocturnal voids decreased from 3.0 to 1.7 and from 3.2 to 2.7, respectively, reflecting a mean decrease of 43% and 12% (P<0.001). The mean duration of the first sleep period increased by 59% (from 2.7 to 4.5 h) in the desmopressin group, compared with an increase of 21% (from 2.5 to 2.9 h) in the placebo group (P<0.001). The mean nocturnal diuresis decreased by 36% (from 1.5 to 0.9 mL/min) in the desmopressin group and by 6% (from 1.7 to 1.5 mL/min) in the placebo group (P<0.001). The mean ratio of night/24-h urine volume decreased by 23% and 1% (P<0.001), and the mean ratio of night/day urine volume decreased by 27% and increased by 3% (P<0.001) for the desmopressin and placebo groups, respectively. In the double-blind treatment period, similar numbers of patients had adverse events; 15 (17%) patients in the desmopressin and 16 (25%) patients in the placebo group. Most adverse events were mild. Serum sodium levels were <130 mmol/L in 10 (4%) patients and this occurred during dose-titration. CONCLUSIONS: Orally administered desmopressin is an effective and well-tolerated treatment for nocturia in men.

Administration, Oral↗
PubMed1997

Lamotrigine versus placebo in the prophylaxis of migraine with and without aura.

Lamotrigine blocks voltage-sensitive sodium channels, leading to inhibition of neuronal release of glutamate. Release of glutamate may be essential in the propagation of spreading cortical depression, which some believe is central to the genesis of migraine attacks. This study compared safety and efficacy of lamotrigine and placebo in migraine prophylaxis in a double-blind randomized parallel-groups trial. A total of 110 patients entered; after a 1-month placebo run-in period, placebo-responders and non-compliers were excluded, leaving 77 to be treated with lamotrigine (n = 37) or placebo (n = 40) for up to 3 months. Initially, lamotrigine therapy was commenced at the full dose of 200 mg/day, but, following a high incidence of skin rashes, a slow dose-escalation was introduced: 25 mg/day for 2 weeks, 50 mg/day for 2 weeks, then 200 mg/day. Attack rates were reduced from baseline means of 3.6 per month on lamotrigine and 4.4 on placebo to 3.2 and 3.0 respectively during the last month of treatment. Improvements were greater on placebo and these changes, not statistically significant, indicate that lamotrigine is ineffective for migraine prophylaxis. There were more adverse events on lamotrigine than on placebo, most commonly rash. With slow dose-escalation their frequency was reduced and the rate of withdrawal for adverse events was similar in both treatment groups.

Adolescent↗
PubMed1997

Double-blind randomized placebo-controlled study of homoeopathic prophylaxis of migraine.

Homoeopathic remedies for migraine are widely available over the counter, statutorily offered by the national health service in the UK, and apparently popular with patients. Do they work? Sixty-three outpatients with migraine with or without aura by IHS criteria entered a 4-month randomized placebo-controlled, double-blind parallel-groups trial of individualized homoeopathic prophylaxis, the first month being baseline with all patients on placebo. Three patients (4.8%) dropped out, leaving 30 in each treatment group. There were chance differences in attack frequency and severity between the groups at baseline (attacks were more frequent but less severe in the placebo group). Both groups improved on therapy, but neither to a great extent on the primary outcome measure of attack frequency (verum: -19%; placebo: -16%). Reduction was mostly in mild attacks on placebo, more in moderate and severe attacks on homoeopathy. Few adverse events were reported. Overall, there was no significant benefit over placebo of homoeopathic treatment. The course of change differed between groups, and suggested that improvement reversed in the last month of treatment on placebo. On this evidence we cannot recommend homoeopathy for migraine prophylaxis, but cannot conclude that it is without effect.

Adult↗
PubMed1997

Double-blind, placebo-controlled, dose-finding study of rizatriptan (MK-462) in the acute treatment of migraine.

Rizatriptan (MK-462) is a potent 5HTID receptor agonist. This multicenter, double-blind, placebo-controlled, outpatient study investigated the clinical efficacy, safety, and tolerability of rizatriptan (2.5, 5, and 10 mg) as a function of dose for acute migraine. Patients with moderate or severe migraine (n = 417) were treated with placebo (n = 67), rizatriptan 2.5 mg (n = 75), 5 mg (n = 130), or rizatriptan 10 mg (n = 145). Headache severity, functional disability, and migraine symptoms were measured immediately before dosing (0) and at 0.5, 1, 1.5, 2, 3, and 4 h post-dose. Patients were permitted to take a second dose of test drug at 2 h if their headache pain was moderate or severe (i.e., placebo initially-->rizatriptan 10 mg as optional second dose; rizatriptan 2.5 mg, 5 mg, or 10 mg initially-->placebo as optional second dose). An upward dose-response relationship was observed among placebo, rizatriptan 2.5 mg, 5 mg, and 10 mg in the primary efficacy measure of proportion of patients reporting pain relief, i.e., a change in headache severity to "no pain or mild pain" at 2 h post-dose. The relationship was evident even at the first recorded timepoint, 30 min, and was statistically significant at 1.5 h and beyond. At the primary timepoint of 2 h after the initial dose, the proportion of patients reporting pain relief was 47.6% for rizatriptan 10 mg; 45.4% for rizatriptan 5 mg; 21.3% for rizatriptan 2.5 mg; and 17.9% for placebo. Seventy percent of patients on rizatriptan 10 mg reported pain relief at 4 h. Patients who took rizatriptan 5 mg and 10 mg were significantly less functionally disabled than those who took placebo at 1.5 and 2 h post-dose. Rizatriptan 10 mg was consistently more effective than 5 mg, although the differences were not statistically significant. The most frequent clinical adverse events were dizziness, somnolence, and asthenia/fatigue. No patients were discontinued for any adverse experiences and there were no serious adverse experiences.

Acute Disease↗
PubMed1999

Efficacy and safety of intravenous acetylsalicylic acid lysinate compared to subcutaneous sumatriptan and parenteral placebo in the acute treatment of migraine. A double-blind, double-dummy, randomized, multicenter, parallel group study. The ASASUMAMIG Study Group.

Two-hundred-and-seventy-eight patients with acute migraine attacks with or without aura were treated in 17 centers with 1.8 g lysine acetylsalicylate i.v. (Aspisol; = 1 g acetylsalicylic acid), 6 mg sumatriptan s.c. or placebo using a double-blind, double-dummy, randomized, multicenter parallel group study design. Two-hundred-and-seventy-five of them fulfilled the criteria for efficacy analysis, corresponding to 119 patients treated with lysine acetylsalicylate (L-ASA), 114 with sumatriptan and 42 with placebo injections. Both treatments were highly effective compared to placebo (p < 0.0001) in decreasing headache from severe or moderate to mild or none (verbal rating scale, VRS, placebo = 23.8%). Sumatriptan showed a significantly (p = 0.001) better response (91.2%) compared to L-ASA (response 73.9%). Of the patients in the L-ASA-group, 43.7% were pain-free after 2 h; 76.3% after sumatriptan and 14.3% after placebo. It took patients on average 12.6 (L-ASA), 8.2 (sumatriptan), and 19.4 h (placebo) to be able to work again. There was no significant difference between treatment groups in recurrence of headache in responders within 24 h (18.2% L-ASA, 23.1% sumatriptan, 20% placebo). Accompanying symptoms (nausea, vomiting; photophobia, phonophobia, and visual disturbances) improved with both verum treatments to a similar extent. L-ASA was significantly better tolerated than sumatriptan (adverse events L-ASA 7.6%, sumatriptan 37.8%). In conclusion, subcutaneous sumatriptan and lysine acetylsalicylate i.v. are effective treatments for patients suffering from migraine attacks. Sumatriptan is more effective, but resulted in more adverse events.

Adult↗
PubMedDate not supplied

Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled, parallel-group study. Naratriptan S2WA3001 Study Group.

OBJECTIVE: To evaluate the efficacy and tolerability of naratriptan, a novel 5-HT1 agonist, in the acute treatment of migraine. DESIGN/METHODS: Six hundred thirteen migraineurs, diagnosed according to International Headache Society criteria, treated a single migraine attack with naratriptan tablets (2.5 mg, 1 mg, 0.25 mg, or 0.1 mg) or placebo in a randomized, double-blind, placebo-controlled, parallel-group study conducted at 54 United States centers. At dosing and at predetermined intervals beginning 30 minutes postdose, patients recorded migraine pain severity, clinical disability, and presence of associated migraine symptoms. Safety measures included adverse events, physical examinations, vital signs, ECGs, and clinical laboratory tests. RESULTS: Headache relief (moderate or severe pain at dosing reduced to mild or no pain) 4 hours postdose was reported in 60% of patients receiving naratriptan 2.5 mg compared with 50%, 35%, 32%, and 34% of patients receiving naratriptan 1 mg, 0.25 mg, 0.1 mg, and placebo, respectively (P < 0.05 naratriptan 2.5 mg and 1 mg versus placebo, 1 mg versus 0.1 mg, and 2.5 mg versus 0.1 mg and 0.25 mg). Clinical disability 4 hours postdose was reported as mild or none for 70% of patients receiving naratriptan 2.5 mg compared with 63%, 47%, 48%, and 48% of patients receiving naratriptan 1 mg, 0.25 mg, 0.1 mg, or placebo, respectively (P < 0.05 naratriptan 2.5 mg and 1 mg versus placebo, 1 mg versus 0.1 mg, and 2.5 mg versus 0.1 mg and 0.25 mg). Four-hour efficacy for absence of nausea, photophobia, and phonophobia was similar to efficacy for headache relief at each dose. The adverse event profile of each dose of naratriptan was similar to that of placebo. No clinically relevant change in any safety measure was reported. CONCLUSIONS: Naratriptan is effective and well tolerated for the acute treatment of migraine. The 2.5-mg dose appears to offer the optimum ratio of efficacy to tolerability.

Acute Disease↗
PubMed2003

Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To assess whether, in children, oral magnesium oxide reduces migrainous headache frequency, severity, and associated features compared to placebo. BACKGROUND: There is no single, safe, widely well-tolerated, and effective prophylactic treatment for all children and adolescents with frequent migrainous headache. DESIGN: Randomized, double-blind, placebo-controlled, parallel-group trial. METHODS: This study was conducted between June 1997 and January 2000 using 7 selected Northern California Kaiser Permanente sites. We recruited children of ages 3 to 17 years who reported a 4-week history of at least weekly, moderate-to-severe headache with a throbbing or pulsatile quality, associated anorexia/nausea, vomiting, photophobia, sonophobia, or relief with sleep, but no fever or evidence of infection. Subjects were randomly assigned to receive either magnesium oxide (9 mg/kg per day by mouth divided 3 times a day with food) (n = 58) or matching placebo (n = 60) for 16 weeks. The number of headache days (days with at least one headache) during each of eight 2-week intervals was chosen to be the primary outcome variable. RESULTS: Of those enrolled, 86 (73%) completed the study (42 received magnesium oxide and 44 placebo); 74 of 192 eligible subjects declined to participate. Baseline information on demographic factors, health status, and headache history was similar comparing the 2 groups. By intention-to-treat analysis, we found a statistically significant decrease over time in headache frequency in the magnesium oxide group (P =.0037) but not in the placebo group (P =.086), although the slopes of these 2 lines were not statistically significantly different from each other (P =.88). The group treated with magnesium oxide had significantly lower headache severity (P =.0029) relative to the placebo group. CONCLUSIONS: This study does not unequivocally determine whether oral magnesium oxide is or is not superior to placebo in preventing frequent migrainous headache in children, but treatment with the active agent did lead to a significant reduction in headache days. Larger trials involving this safe, appealing complementary therapy are needed.

Administration, Oral↗
PubMed1999

Conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm: the effect of no treatment and high-dose amiodarone. A randomized, placebo-controlled study.

BACKGROUND: Spontaneous conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm occurs commonly and is not affected by low-dose amiodarone treatment. METHODS: In a randomized, placebo-controlled trial of 100 patients with paroxysmal atrial fibrillation of recent onset (<48 h) we compared the effects of treatment with continuous intravenous amiodarone 125 mg per hour (total 3 g) and intravenous placebo. Patients in the placebo group who did not convert to normal sinus rhythm within 24 h were started on amiodarone therapy. RESULTS: Conversion to normal sinus rhythm occurred within 24 h in 32 of 50 patients (64%) in the placebo group, most of whom converted within 8 h. Lower conversion rates were observed in patients with hypertension, ischaemic heart disease or congestive heart failure and in patients with echocardiographic findings of left atrial diameter above 45 mm, ejection fraction below 45% or significant mitral regurgitation. However, in most patients these clinical or echocardiographic risk factors of decreases in conversion rate were not present. In such patients the spontaneous conversion rate was approximately 90%. The conversion rate during 24 h of treatment in the amiodarone group was 92% (P=0.0017, compared to the placebo group). In this group, the conversion rate was largely unaffected by baseline characteristics. Of the 18 patients who did not convert with placebo, 15 (85%) converted after being crossed over to amiodarone. All patients not responding to high-dose amiodarone were in chronic atrial fibrillation within 1 month. In patients still in atrial fibrillation after 8 h of treatment, the pulse rate decreased significantly more in the amiodarone as compared to the placebo group (83+/-15 vs 114+/-20 beats. min(-1), P=0.0014). CONCLUSION: The spontaneous conversion of recent onset paroxysmal atrial fibrillation is high and approaches 90% in specific clinical and echocardiographically defined subgroups. Intravenous high-dose amiodarone safely facilitates conversion of paroxysmal atrial fibrillation. However, such treatment should be reserved for patients with unfavourable risk factor profiles, not converting during 8 h of observation or requiring rate control.

Aged↗
PubMed2001

Dipyridamole in chronic stable angina pectoris; a randomized, double blind, placebo-controlled, parallel group study.

BACKGROUND: Oral dipyridamole induces accumulation of endogenous adenosine, which in a hypoxic milieu exerts experimentally an angiogenic effect on coronary collateral circulation. A meta-analysis of 13 randomized placebo-controlled trials published between 1960 and 1992 showed evidence of benefit for dipyridamole in the treatment of angina pectoris, especially with longer duration of treatment. Aim To assess the efficacy and safety of dipyridamole in the treatment of patients with chronic stable angina in a large scale, international, randomized, placebo-controlled, parallel group study. METHODS: Four hundred patients with chronic stable angina pectoris and a positive treadmill exercise test were randomized to receive either modified release dipyridamole (200 mg b.i.d. p.o., n=198) or corresponding placebo (n=202), for 24 weeks as an add-on to conventional antianginal therapy and for 4 additional weeks as monotherapy--the latter after withdrawal of standard treatment with calcium antagonists and/or beta-blockers and/or long-acting (prophylactic) nitrates. RESULTS: Of the 198 patients randomized to dipyridamole, 134 completed the add-on and only 12 the monotherapy phase. Of the 202 patients randomized to placebo, 162 reached the add-on and only 12 the monotherapy phase. Serious adverse events occurred in 15 patients with dipyridamole and in 12 with placebo (7.6% vs 6.0, P=0.52). Increase over the baseline treadmill exercise test was similar in the treatment groups at each stage of the trial for all the main efficacy parameters: total treadmill exercise test duration; time to first anginal pain (except for a -13 s difference in favour of placebo at week 24;P=0.040); time to ST segment depression >0.1 mVolt (except for a +21 s difference in favour of dipyridamole at week 8;P=0.024; this latter difference was totally attributable to patients with lower exercise tolerance--Bruce stage II at study entry). CONCLUSION: In patients with chronic stable angina treated with regular antianginal background medication, the use of oral dipyridamole is safe and well tolerated. Antianginal and antiischaemic efficacy, as assessed by exercise testing, is comparable to placebo, except for a beneficial effect on time to ischaemia after 2 months, totally attributable to patients with lower exercise tolerance at study entry.

Administration, Oral↗
PubMed2005

Colchicine treatment of alcoholic cirrhosis: a randomized, placebo-controlled clinical trial of patient survival.

BACKGROUND & AIMS: Colchicine improved survival and reversed cirrhosis in several small clinical trials. We compared the efficacy and safety of long-term colchicine, as compared with placebo, in patients with advanced alcoholic cirrhosis. METHODS: Five hundred forty-nine patients with advanced (Pugh B or C) alcoholic cirrhosis were randomized to receive either colchicine 0.6 mg twice per day (n = 274) or placebo (n = 275). Treatment lasted from 2 to 6 years. The primary outcome was all-cause mortality. Secondary outcomes were liver-related morbidity and mortality. Liver biopsy was requested prior to entry and after 24 months of treatment. RESULTS: Attendance at scheduled clinic visits and adherence with study medication were similar in colchicine and placebo groups. Alcohol intake was less than 1 drink per day in 69% of patients. In an intention-to-treat analysis, all-cause mortality was similar in colchicine (49%) and placebo (45%) patients (P = .371). Mortality attributed to liver disease was 32% in colchicine and 28% in placebo patients (P = .337). Fewer patients receiving colchicine developed hepatorenal syndrome. In 54 patients with repeat liver biopsies after 24 or more months of treatment, cirrhosis improved to septal fibrosis in 7 patients (3 colchicine, 4 placebo) and to portal fibrosis in 1 patient (colchicine). CONCLUSIONS: In patients with advanced alcoholic cirrhosis, colchicine does not reduce overall or liver-specific mortality. Liver histology improves to septal fibrosis in a minority of patients after 24 months of treatment, with similar rates of improvement in patients receiving placebo and colchicine. Colchicine is not recommended for patients with advanced alcoholic cirrhosis.

Colchicine↗
PubMed2004

Randomized, double-blind, placebo-controlled trial to evaluate efficacy of ketodiet in predialytic chronic renal failure.

OBJECTIVE: To assess whether a ketodiet, a combination of ketoanalogs of essential amino acids (KAs) and a very low-protein diet, retards progression of chronic renal failure and maintains nutritional status. DESIGN: A prospective, randomized, double-blind, placebo-controlled trial. SETTING: Nephrology outpatient department in Northern Railways Central Hospital, New Delhi, India. PATIENTS: Thirty-four patients in predialytic stages of chronic renal failure (CRF), randomized to 2 comparable groups in terms of age, sex distribution, blood pressure control, etiology, use of angiotensin converting enzyme inhibitors, serum creatinine, glomerular filtration rate (GFR), and body mass index (BMI). INTERVENTION: Subjects randomly received either 0.6 g/kg/d protein plus placebo (n = 16) or 0.3 g/kg/d protein plus tablets of KAs (Ketosteril; Fresenius Kabi, Germany) (n = 18) for 9 months. A dietician administered the diet as well as the KAs or the placebo to the patients. OUTCOME MEASURES: Changes in GFR and renal and nutritional parameters were measured. RESULTS: Mean (+/- SD) GFR measured by the 99mTc-DTPA (99 m technetium diethylenetri-aminepenta-aceticacid) plasma sample method was unchanged in the ketodiet group: 28.1 +/- 8.8 (before) and 27.6 +/- 10.1 mL/min/1.73 m2 (after the study) (P =.72). However, it significantly decreased from 28.6 +/- 17.6 to 22.5 +/- 15.9 mL/min/1.73 m2 in the placebo group (P =.015). Serum creatinine before and after the study in the ketodiet group was 2.26 +/- 1.03 mg/dL and 2.07 +/- 0.8 mg/dL (P =.90) and in the placebo group was 2.37 +/- 0.85 and 3.52 +/- 2.9 mg/dL (P =.066), respectively. In both groups the mean BMI did not change from 25.4 +/- 4.2 to 24.5 +/- 4.2 kg/m2 (P =.46) for ketodiet and from 25.0 +/- 6.8 to 23.9 +/- 4.1 kg/m2 (P =.39) for the placebo group. Serum total proteins decreased significantly (P =.038) in the placebo group, and serum albumin showed a trend (P =.061) toward reduction, whereas both of these parameters were maintained in the ketodiet group. CONCLUSION: Over a 9-month period, very low-protein diet supplemented with ketoanalogs helped CRF patients to preserve GFR and maintain BMI. KAs were safe and efficacious in retarding the progression of renal failure and preserving the nutritional status of CRF patients.

Amino Acids, Essential↗
PubMed2003

Effects of venlafaxine, buspirone, and placebo on colonic sensorimotor functions in healthy humans.

BACKGROUND & AIMS: We have shown that venlafaxine-XR, a serotonin (5-HT) and norepinephrine reuptake inhibitor, enhanced gastric accommodation, whereas buspirone, a 5-HT(1A) receptor agonist, reduced postprandial symptoms after a fully satiating meal. Our aim was to compare the effects of venlafaxine, buspirone, and placebo on colonic sensorimotor functions in healthy adults. METHODS: In this randomized, double-blind, parallel-group, placebo-controlled trial of 60 healthy adults, we assessed the effects of oral venlafaxine, 150 mg; buspirone, 20 mg; and placebo on colonic sensorimotor functions. RESULTS: Venlafaxine increased colonic compliance relative to placebo; thus it decreased the intracolonic balloon pressure at half-maximum volume (P = 0.001) and altered the overall shape of the compliance curve, beta (P = 0.01). Venlafaxine also decreased fasting colonic tone (P = 0.02) and the tonic response to a meal (P = 0.003) compared with placebo; no differences in high amplitude phasic contractile events were observed. Pressure thresholds for first sensation (P = 0.1) and gas (P = 0.07) were not statistically significant with venlafaxine. The increase in pain scores per unit pressure during phasic distentions were affected by treatment (P = 0.02), with smallest changes on venlafaxine and highest on placebo. Buspirone did not significantly alter colonic compliance, tone, or sensation relative to placebo. CONCLUSIONS: Venlafaxine alters colonic compliance and tone, and tends to reduce sensation during colonic distention in healthy humans. These data support the need for further clinical and physiologic studies of venlafaxine in colonic disorders affecting motor and possibly sensory functions.

Adult↗
PubMed2004

Clinical, double-blind, placebo-controlled study investigating the combination of acetylsalicylic acid and pseudoephedrine for the symptomatic treatment of nasal congestion associated with common cold.

It was the aim of this clinical study to demonstrate the efficacy of 1000 mg acetylsalicylic acid (ASA, CAS 50-78-2) in combination with 60 mg pseudoephedrine (PSE, CAS 90-82-4), compared with placebo, in the symptomatic treatment of nasal congestion associated with the common cold. A further aim was to demonstrate the efficacy of 500 mg ASA + 30 mg PSE and of 1000 mg paracetamol (CAS 103-90-2) + 60 mg PSE (active control) in the symptomatic treatment of nasal congestion. The study was designed as a randomized, two-center, double-blind, double-dummy, placebo-controlled, parallel-group, single-dose efficacy and safety trial over 6 h and was carried out in the USA. In total, at two centers, 643 patients who had a history and diagnosis of acute upper respiratory tract infection (URTI), were included; they showed symptoms such as nasal congestion, scratchy/sore throat, headache, generalized muscle ache, earache, runny nose, fever, sneezing etc. The investigational drugs ASA and PSE were both provided as granules in sachets and the granules were dissolved in water before administration; the combined preparation of paracetamol + PSE was administered as commercially available tablets encapsulated for blinding. For all preparations, matching placebos were provided. The primary efficacy variable was the area under the curve for differences from baseline on a nasal congestion scale in the first 2 h after treatment. To be eligible for the study, otherwise healthy volunteers were to present with nasal stuffiness of recent onset that reached a score of at least 6 on the 11-point scale for nasal congestion (0 = not stuffy, 10 = very stuffy). The primary analysis of the primary efficacy variable was calculated by analysis of variance including treatment group, severity (moderate/severe) and center as main strata. The analysis was performed using the intent-to-treat population. All active treatments proved to be statistically significantly superior to placebo with regard to the primary efficacy variable. Significant superiority of active treatment compared with placebo could also be demonstrated for an interval of up to 6 h after intake of the drug and for the relief of nasal congestion. The lower dose did not reveal significant different results compared with placebo for relief of nasal congestion in patients with a severe nasal congestion score at baseline. As well in patients with moderate nasal congestion score (NCS) at start of the study the difference from baseline in the NCS compared with placebo was not statistically significant. Thus a trend towards better efficacy in the higher dose could be assumed. No difference was found between 1000 mg ASA + 60 mg PSE and the active control. There were no differences between the two centers. The treatment proved to be safe and well tolerated, without relevant differences between the four treatment groups. Main adverse events were found to be related to the upper respiratory tract infection or were of gastrointestinal nature. In conclusion, the combination of ASA with PSE can be considered as an effective and safe remedial for the symptomatic treatment of the nasal congestion during URTI.

Acetaminophen↗
PubMed2003

The validity of the depression rating scales in discriminating between citalopram and placebo in depression recurrence in the maintenance therapy of elderly unipolar patients with major depression.

The World Federation of Societies of Biological Psychiatry guidelines for treatment of unipolar major depression has recommended three depression rating scales for evaluating outcome: The Hamilton Depression Rating Scale (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Bech-Rafaelsen Melancholia Scale (MES). In this study we evaluated the ability of these scales to differentiate between citalopram and placebo in the recurrence prevention of unipolar depression. The study is a psychometric reexamination of a trial on the efficacy of citalopram versus placebo in the maintenance therapy of elderly patients with unipolar depression. Internal validity (the Cronbach coefficient alpha, the Loevinger coefficient of homogeneity, and factor analysis) of the three scales has been examined to evaluate their unidimensionality. In the outcome analysis for depression recurrence, the conventional cutoff scores of the three scales are used. In total, 60 patients received citalopram and 61 patients received placebo in the maintenance phase of 48 weeks. The results showed that the internal validity was higher for MES and MADRS than for HAM-D. Using the MADRS, 67.2 % of the patients on placebo and 31.6 % of the patients on citalopram developed a depression recurrence (ratio 2.12); using HAM-D17, 42.6 % on placebo and 13.3 % on citalopram developed a depression recurrence (ratio 3.20); and using the MES, 34.4 % on placebo and 11.7 % on citalopram developed a depression recurrence (ratio 2.94). The conventional cutoff scores of HAM-D17 and MES for depression recurrence indicated a ratio between citalopram and placebo of around 3, while the conventional cutoff scores of MADRS for depression recurrence indicated a ratio of only around 2. In future trials on the recurrence prevention of unipolar depression, a cutoff score of 25 rather than 22 on the MADRS is recommended.

Aged↗
PubMed2004

Polysomnography during withdrawal with clomethiazole or placebo in alcohol dependent patients--a double-blind and randomized study.

INTRODUCTION: The present study was designed to assess if the routine application of clomethiazole to ameliorate withdrawal symptoms in chronic alcohol dependent patients perpetuates sleep disturbances. METHODS: Twenty inpatients with alcohol dependence according to DSM-IV criteria received clomethiazole or placebo in a double-blind, randomized design upon admission. 11 patients were randomized to the clomethiazole group and 9 patients to the placebo group. During the first 5 days of treatment the patients received either clomethiazole (1st day: 3 x 384 mg, 2nd day: 4 x 384 mg, 3rd day: 3 x 384 mg, 4th day: 2 x 384 mg and 5th day: 1 x 384 mg) or placebo capsules at constant intervals. The patients spent two consecutive nights in the sleep laboratory at each of three assessment times: the first time at the beginning of abstinence (night 1 and 2, T0), the second time 6 days later (i. e. after 5 days of treatment and one day of discontinuation of clomethiazole or placebo: nights 6 and 7, T1) and the third time after 13 days (nights 13 and 14, T2). The first night at each of the three assessment times was an adaptation night. RESULTS: During the first two weeks of abstinence, the analysis of variance demonstrated a significant variation of Rapid Eye Movement (REM) sleep variables in the clomethiazole group. The placebo group showed no such variation. Clomethiazole evidently had a pronounced REM sleep suppressing effect, whereas the discontinuation of clomethiazole led to a REM sleep rebound. Furthermore, analysis of sleep continuity and sleep architecture variables showed that the clomethiazole group had significantly disturbed sleep at T1 in comparison to the placebo group. Simultaneous statistical testing with alcohol intake as covariate reduced the test power so that contrasts between the groups became nonsignificant. CONCLUSIONS: The REM sleep results are in line with earlier findings that REM sleep disinhibition in primary alcohol dependency is partly due to a REM sleep rebound after withdrawal from medication. Differences in the polysomnographic variables of sleep continuitiy and sleep architecture at T0 and T1 found between the clomethiazole and the placebo patients correspond to rebound insomnia following discontinuation of clomethiazole. Our findings indicate that drugs enforcing GABAergic neurotransmission may perpetuate the neuroadaptative effects caused by chronic alcohol consumption.

Adult↗