Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study

BACKGROUND: At present there are only intriguing and preliminary clinical results regarding the efficacy of metadoxine (pyridoxol L-2-pyrrolidone-5-carboxylate) in acute alcohol intoxication. The present study was planned with the aim of investigating the effectiveness of metadoxine in the management of patients affected by acute ethanol intoxication. METHODS: A double-blind, randomized, multicenter, placebo-controlled trial was carried out on 58 patients of both sexes with acute ethanol intoxication. Patients were treated with a single dose of 900-mg intravenous metadoxine (n = 29) or with placebo (n = 29). Patients were clinically and biochemically evaluated at 0.5, 1, 2, 3, 6, 9, and 12 hr after treatment. RESULTS: Treatment with metadoxine significantly decreased the half-life of ethanol in blood (from 6.70 +/- 1.84 to 5.41 +/- 1.99 hr; p < 0.013) and showed a faster rate of ethanol elimination. The effects on ethanol half-life in blood were accompanied by a faster onset of recovery from intoxication, defined as the time of the transition of blood ethanol levels to the immediately lower range defined by intoxication categories (in g/liter: 0 to 0.5, absent; 0.51 to 1.0, mild; 1.1 to 2.5, moderate; >2.5, severe). Thus the median time to onset of recovery was 0.95 hr with metadoxine and 2.34 hr with placebo (p = 0.013). The effects of treatment on blood alcohol levels were paralleled by a significant decrease in the rating of the toxic clinical symptomatology. At 2 hr the improvement of toxic symptoms (in percent of maximum possible) was 68 +/- 28 vs. 44 +/- 27% in controls (p < 0.002). CONCLUSIONS: In patients with acute ethanol intoxication metadoxine accelerated the elimination of ethanol from blood, which led to faster recovery from intoxication, and improved the behavioral toxic symptomatology. Metadoxine could be helpful in the management of acute ethanol intoxication.     

Effects of anthocyanins on blood pressure and stress reactivity: a double-blind randomized placebo-controlled crossover study

High intakes of flavonoids are associated with reduced cardiovascular risk, and flavonoids such as cocoa and soy protein isolate have shown beneficial effects on blood pressure (BP). Anthocyanins constitute a flavonoid subgroup consumed in regular diets, but few studies have assessed the antihypertensive potential of anthocyanins. We aimed to assess whether high concentrations of relatively pure anthocyanins reduce BP and alter cardiovascular and catecholamine reactivity to stress. A total of 31 healthy men between 35-51 years of age with screening BP >140/90 mm Hg, not on antihypertensive or lipid-lowering medication, were randomised in a double-blind crossover study to placebo versus 320-mg anthoycanins twice daily. Treatment duration was 4 weeks, with a 4-week washout. Sitting and supine BP measurements, ambulatory BP recording and stress reactivity were assessed and analyzed by a paired sample t-test. In all, 27 patients completed all visits. Sitting systolic BP (primary endpoint) was 133 mm Hg after placebo versus 135 mm Hg after anthocyanin treatment (P=0.25). Anthocyanins did neither affect semiautomatic oscillometric BP measurements in the sitting or supine position nor 24-h ambulatory BP. No significant differences in stress reactivity were found across treatment periods. Overall, we conclude that high concentrations of these relatively pure anthocyanins do not reduce BP in healthy men with a high normal BP.     

Irbesartan plus low-dose propranolol versus low-dose propranolol alone in cirrhosis: a placebo-controlled, double-blind study

OBJECTIVES:  Angiotensin II receptor antagonists have been shown to moderately lower portal pressure in some patients with cirrhosis but may have adverse effects on kidney function. This study aimed at comparing the effects of a combined treatment using irbesartan plus propranolol with propranolol monotherapy on portal pressure and kidney function in patients with cirrhosis.
METHODS:  Thirty-two patients were included (Child A/B/C: 13/18/1, etiology: 16 alcohol, 13 viral, 3 other; bilirubin 1.4 ± 1.1 mg/dL, creatinine 0.86 ± 0.20 mg/dL, baseline hepatic venous pressure gradient 18.7 ± 5.3 mmHg). All patients received 20 mg propranolol b.i.d. Additionally, they randomly received either placebo (N = 15) or irbesartan (step-up dosage titration up to 300 mg/d, N = 17). Patients were followed at weekly intervals, re-evaluation of hepatic venous pressure gradient (HVPG) was performed after 8 wk.
RESULTS:  One patient in the propranolol/irbesartan group was excluded due to variceal bleeding. No other adverse events occurred. Portal pressure declined in both groups (propranolol/irbesartan group 19.6 ± 1.5 mmHg to 16.6 ± 1.2 mmHg, P = 0.037, propranolol/placebo group 17.8 ± 1.1 mmHg to 15.1 ± 1.2 mmHg, P = 0.019). Sodium excretion significantly increased in the propranolol/irbesartan group (from 122 ± 20 mmol/d to 230 ± 23 mmol/d, P = 0.045), but not in the propranolol/placebo group.
CONCLUSIONS:  Combination treatment of propranolol plus irbesartan is well tolerated in cirrhotic patients when titrating the angiotensin II antagonist in a step-up manner, and it increases sodium excretion in patients with compensated or moderately decompensated cirrhosis. Addition of irbesartan has no effect on portal pressure.     

Effects of acotiamide on esophageal motility in healthy subjects: a randomized,double-blind,placebo-controlled crossover study

Background

Acotiamide is a new drug that exhibits prokinetic activity by enhancing the release of acetylcholine. However, its effects on esophageal motility currently remain unknown. Therefore, we herein investigated the effects of acotiamide on esophageal motility in healthy, asymptomatic subjects.

Methods

Thirty healthy subjects received 100 mg of acotiamide or placebo three times a day for 7 days separated by a 28-day washout period in a randomized, double-blind, placebo-controlled crossover study. On the seventh day of treatment, esophagogastric junction pressure, integrated relaxation pressure, and primary peristalsis were assessed using high-resolution manometry.

Results

Esophagogastric junction pressure was significantly higher in the acotiamide group (median 28.2 mmHg) than in the placebo group (24.0 mmHg), whereas no significant differences were observed in integrated relaxation pressure, the distal contractile integral, or contraction patterns between the two groups. Among 13 healthy subjects with peristaltic abnormalities, no significant differences were noted in integrated relaxation pressure or the distal contractile integral between the acotiamide and placebo groups; however, the esophagogastric junction pressure (acotiamide 23.4 mmHg; placebo 21.7 mmHg) significantly increased, the contraction pattern significantly improved, and the frequency of esophageal peristaltic abnormalities significantly decreased in the acotiamide group.

Conclusion

Acotiamide improves the peristaltic pattern in patients with peristaltic abnormalities by decreasing weak peristalsis with a small break.

     

Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study

CONTEXT: Hypopituitarism in women is characterized by profound androgen deficiency due to a loss of adrenal and/or ovarian function. The effects of testosterone replacement in this population have not been reported. OBJECTIVE: The objective of the study was to determine whether physiologic testosterone replacement improves bone density, body composition, and/or neurobehavioral function in women with severe androgen deficiency secondary to hypopituitarism. DESIGN: This was a 12-month randomized, placebo-controlled study. SETTING: The study was conducted at a general clinical research center. STUDY PARTICIPANTS: Fifty-one women of reproductive age with androgen deficiency due to hypopituitarism participated. INTERVENTION: Physiologic testosterone administration using a patch that delivers 300 microg daily or placebo was administered. MAIN OUTCOME MEASURES: Bone density, fat-free mass, and fat mass were measured by dual x-ray absorptiometry. Thigh muscle and abdominal cross-sectional area were measured by computed tomography scan. Mood, sexual function, quality of life, and cognitive function were assessed using self-administered questionnaires. RESULTS: Mean free testosterone increased into the normal range during testosterone administration. Mean hip (P = 0.023) and radius (P = 0.007), but not posteroanterior spine, bone mineral density increased in the group receiving testosterone, compared with placebo, as did mean fat-free mass (P = 0.040) and thigh muscle area (P = 0.038), but there was no change in fat mass. Mood (P = 0.029) and sexual function (P = 0.044) improved, as did some aspects of quality of life, but not cognitive function. Testosterone at physiologic replacement levels was well tolerated, with few side effects. CONCLUSIONS: This is the first randomized, double-blind, placebo-controlled study to show a positive effect of testosterone on bone density, body composition, and neurobehavioral function in women with severe androgen deficiency due to hypopituitarism.     

Melatonin improves sleep in asthma: a randomized, double-blind, placebo-controlled study

Disturbed sleep is common in asthma. Melatonin has sleep-inducing activity and reportedly affects smooth muscle tone and inflammation. The aim of this study was to evaluate the effect of melatonin on sleep in patients with mild and moderate asthma. This was a randomized, double-blind, placebo-controlled study. Twenty-two consecutive women with asthma were randomized to receive melatonin 3 mg (n = 12) or placebo (n = 10) for 4 weeks. Sleep quality and daytime somnolence were assessed by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale, respectively. Pulmonary function was assessed by spirometry. Use of relief medication, asthma symptoms, and morning and evening peak expiratory flow rate were recorded daily. Melatonin treatment significantly improved subjective sleep quality, as compared with placebo (p = 0.04). No significant difference in asthma symptoms, use of relief medication and daily peak expiratory flow rate was found between groups. We conclude that melatonin can improve sleep in patients with asthma. Further studies looking into long-term effects of melatonin on airway inflammation and bronchial hyperresponsiveness are needed before melatonin can be recommended in patients with asthma.     

Effect of oral melatonin on the procoagulant response to acute psychosocial stress in healthy men: a randomized placebo-controlled study

Abstract:  Acute mental stress is a potent trigger of acute coronary syndromes. Catecholamine-induced hypercoagulability with acute stress contributes to thrombus growth after coronary plaque rupture. Melatonin may diminish catecholamine activity. We hypothesized that melatonin mitigates the acute procoagulant stress response and that this effect is accompanied by a decrease in the stress-induced catecholamine surge. Forty-five healthy young men received a single oral dose of either 3 mg melatonin (n = 24) or placebo medication (n = 21). One hour thereafter, they underwent a standardized short-term psychosocial stressor. Plasma levels of clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, and catecholamines were measured at rest, immediately after stress, and 20 min and 60 min post-stress. The integrated change in D-dimer levels from rest to 60 min post-stress differed between medication groups controlling for demographic and metabolic factors ( P  = 0.047,      = 0.195). Compared with the melatonin group, the placebo group showed a greater increase in absolute D-dimer levels from rest to immediately post-stress ( P  = 0.13;      = 0.060) and significant recovery of D-dimer levels from immediately post-stress to 60 min thereafter ( P  = 0.007;      = 0.174). Stress-induced changes in FVII:C, FVIII:C, fibrinogen, and catecholamines did not significantly differ between groups. Oral melatonin attenuated the stress-induced elevation in the sensitive coagulation activation marker D-dimer without affecting catecholamine activity. The finding provides preliminary support for a protective effect of melatonin in reducing the atherothrombotic risk with acute mental stress.     

Palifermin for the reduction of acute GVHD: a randomized, double-blind, placebo-controlled trial

This prospective, randomized, double-blind, placebo-controlled study evaluated the efficacy of palifermin to reduce the incidence of severe (grade 3-4) acute GVHD after myeloablation and allo-SCT. Adults who received allo-SCT for hematologic malignancies received placebo or palifermin 60?μg/kg daily on three consecutive days before conditioning and a single dose of 180?μg/kg after conditioning, but often 1 or 2 days before allo-SCT. Subjects received MTX (plus CYA or tacrolimus) on days 1, 3, 6 and 11. Acute GVHD was evaluated once weekly and oral mucositis was evaluated daily. Subjects were randomly assigned to placebo (n=78) or palifermin (n=77). Conditioning included TBI in approximately half of the subjects (48% placebo, 51% palifermin). The primary efficacy end point, subject incidence of grade 3-4 acute GVHD, was similar between treatment groups (17% placebo, 16% palifermin). Grade 3-4 oral mucositis (73% placebo, 81% palifermin) and other secondary efficacy end points were similar between treatment groups. The most commonly reported treatment-related adverse events were skin/s.c. events such as rash, pruritus, and erythema. This exploratory study of acute GVHD after myeloablation and allo-SCT did not provide evidence of a treatment effect with this dosing regimen of palifermin.     

The application of nebivolol in essential hypertension: a double-blind, randomized, placebo-controlled study.

This randomized, double-blind, placebo-controlled study investigated the effects of nebivolol on blood pressure, plasma renin and vasoactive hormones (aldosterone and atrial natriuretic peptide) and the heart (arrhythmias, left ventricular mass and ejection fraction) in 32 hypertensive Chinese patients aged 25-65 years. Patients received either placebo (3 men, 11 women) or nebivolol 5 mg (5 men, 13 women) once daily for 4 weeks. In the nebivolol group, a significant decrease in blood pressures (P less than 0.001) and heart rate (P less than 0.01) was seen. Nebivolol therapy also suppressed plasma renin and aldosterone concentration (P less than 0.02) but increased plasma atrial natriuretic peptide levels (P less than 0.03). No significant changes in routine blood biochemistry were demonstrated in either group. There was a tendency for left ventricular mass to decline, and left ventricular ejection fraction to rise during nebivolol therapy, but these changes did not reach statistical significance. There was no significant change in ectopic activity. None of the 32 subjects had adverse experiences requiring cessation of therapy. In conclusion, nebivolol in a dose of 5 mg daily is effective and well tolerated in patients with essential hypertension. It suppresses plasma renin and aldosterone and stimulates plasma atrial natriuretic peptide.     

Fluoxetine vs. propranolol in the treatment of vasovagal syncope: a prospective, randomized, placebo-controlled study.

AIMS: To compare the therapeutic efficacy of placebo, propranolol, and fluoxetine in patients with vasovagal syncope (VVS). METHODS AND RESULTS: Ninety-six consecutive patients with VVS were randomized to treatment with placebo, propranolol, or fluoxetine and followed-up for 6 months. Before and during treatment, they reported their syncopal and presyncopal episodes and graded their well-being, expressed as the general evaluation of life, general activities, and everyday activities (each scaled from 1 = very good to 5 = very bad). Two patients refused follow-up. Among the remaining 94, no difference between groups was observed regarding the distribution of time of vasovagal events (syncopes or presyncopes) during follow-up (log-rank test). No difference was also observed when syncopes and presyncopes were assessed separately. Eighteen patients discontinued therapy. Among the remaining 76 ('on-treatment' analysis), the mean time to a vasovagal episode (syncope or presyncope) was significantly longer in the fluoxetine group when compared with the two other groups (log-rank test, P < 0.05). A significant difference in favour of fluoxetine was also observed regarding presyncopes. The difference between groups regarding the syncope-free period was not significant. During therapy, patients' well-being was improved (decreased) only in the fluoxetine-group (13.4 +/- 0.7 vs. 15.4 +/- 0.9 before treatment, P < 0.01). CONCLUSION: Fluoxetine seems to be equivalent to propranolol and placebo in the treatment of VVS. However, it improves patients' well-being and might be more effective in reducing presyncopes and total vasovagal events in some patients with recurrent VVS.     

Octreotide in hepatorenal syndrome: a randomized,double-blind,placebo-controlled,crossover study

The hepatorenal syndrome (HRS) is related to vasoconstriction of the renal cortex induced by systemic hypovolemia that follows splanchnic vasodilatation as the primary event in the cascade of hemodynamic changes associated with portal hypertension. We evaluated the effects of octreotide, a splanchnic vasoconstrictor, on HRS in cirrhotic patients. We compared the effects of octreotide infusion (50 microg/h) to placebo using a randomized, double-blind, cross-over design over 2, 4-day periods. Nineteen patients were included, and 14 patients could complete the 2 phases of the study (group 1: placebo first; n = 8 and group 2: octreotide first; n = 6) The end point of the study was to evaluate improvement in renal function as defined by a 20% decrease in serum creatinine value after a 4-day treatment as compared with baseline. In all the patients, a normal central venous pressure was maintained by daily intravenous administration of 2 units of albumin. The 2 groups were similar with regard to demographic data and liver and kidney function parameters at baseline. Improvement in renal function was observed in 2 patients after the placebo and 1 patient after octreotide infusion in group 1 and in 2 patients after octreotide infusion and 1 patient after placebo in group 2 (P = not significant). In addition, treatment with octreotide infusion did not result in significant changes in creatinine clearance, daily urinary sodium, plasma renin activity, plasma aldosterone and glucagon levels, or renal and mesenteric artery resistance indices as measured by Doppler ultrasonography. In conclusion, the present study demonstrates that, under our experimental conditions, octreotide infusion combined with albumin is not effective for the treatment of HRS in cirrhotic patients.     

Effects of melatonin supplementation on disease activity,oxidative stress,inflammatory, and metabolic parameters in patients with rheumatoid arthritis: a randomized double-blind placebo-controlled trial

Clinical Rheumatology - Considering the pathologic significance of inflammation and oxidative stress in rheumatoid arthritis (RA) as well as the antioxidant, anti-inflammatory and hypolipidemic...     

Chagas’ cardioneuropathy: Effects of ganglioside treatment on stress-induced arrhythmias. A randomized,double-blind,placebo-controlled study

Chagas’ disease is manifested by cardiovascular and autonomic nervous system disorders with arrhythmias and sudden death. This paper reports the results of an analysis of the mean total arrhythmias (MTA), calculated as the sum of arrhythmias counted after cough, hyperventilation, and postural stress tests, that was conducted as part of a randomized, double-blind, placebo-controlled study. This analysis evaluated the effect on MTA of eight weeks of treatment with Cronassial^® (mixed gangliosides) in a 58-patient study, conducted under a U.S. Food and Drug Administration-approved investigational New Drug Application. Results demonstrated the following: (1) patients receiving placebo during the first four weeks increased in MTA from 0.39 to 1.69, then decreased to 0.69 following four weeks of ganglioside therapy; (2) patients receiving gangliosides in the first four weeks decreased in MTA from 2.70 to 0.41; and (3) the subset of these latter patients who continued with ganglioside therapy for an additional four weeks had a further decrease to 0.36 after a total of eight weeks of ganglioside treatment, while the remaining patients who changed from gangliosides to placebo after week 4 returned to a higher MTA of 1.15. Comparisons between ganglioside- and placebo-treated patients were statistically significant (p<0.05) at both four and eight weeks, favoring ganglioside therapy. In conclusion, gangliosides reduced the mean number of stress-induced arrhythmias in chronic chagasic patients. This effect may be due to gangliosides’ ability to stabilize autonomic control of the heart.     

Alendronate prevents bone loss in patients with acute spinal cord injury: a randomized, double-blind, placebo-controlled study

CONTEXT: Patients who sustain an acute spinal cord injury (SCI) experience rapid dramatic reductions in bone mineral density (BMD), especially marked in sublesional areas and sometimes leading to hypercalcemia and hypercalciuria, as well as increased fracture risk. OBJECTIVE: In this prospective, double-blind, randomized, placebo-controlled study, we evaluated the hypothesis that oral alendronate administration would preserve BMD when administered soon after acute SCI. PATIENTS AND INTERVENTION: Thirty-one patients with acute SCI were randomly allocated to receive oral alendronate 70 mg/wk or placebo, within 10 d of acute SCI, for 12 months. MAIN OUTCOME MEASUREMENTS: At entry and at 3, 6, 12, and 18 months, total body bone density, lumbar and hip BMD, ultrasound of the calcaneus, 24-h urinary calcium, and serum C-telopeptide (betaCTX) were measured. RESULTS: At study entry, patients in the two groups were well matched for age, gender, severity of neurological deficit, BMD, urinary calcium, and betaCTX. BMD indices declined steadily in the placebo group, and this effect was attenuated significantly by alendronate. After 12 months, there was a 5.3% difference (P<0.001) in total body BMD and a 17.6% difference (P<0.001) in the total hip BMD between the two groups. Alendronate compared with placebo induced significant (P<0.001) reductions in urinary calcium excretion and serum betaCTX. No treatment-related side effects were noted. CONCLUSIONS: We conclude that alendronate therapy, 70 mg/wk, initiated soon after acute SCI, prevents bone loss and is not associated with side effects.