Double blind

Acetyl-i-carnitine (4) is marketed in Italy for dementia as of this writing it is also in Phase III clinical trials in the United States and Europe. In a double-blind, placebo-controUed clinical trial over a one-year period involving 130 patients with clinically diagnosed AD, a slower rate of deterioration in 13 of the 14 outcome measures was observed in the dmg-treated group (28). Earfler smaller scale pilot studies in demented patients had also shown some improvement of various behavioral and cognitive functions (29). 

Aniracetam (6), launched in 1993 in both Japan and Italy for the treatment of cognition disorders, is in Phase II trials in the United States as of this writing. In clinical studies it has been shown to cause some improvement in elderly patients with mild to moderate mental deterioration (63), and in geriatric patients with cerebral insufficiency (64). In a multicenter double-blind placebo-controUed trial involving 109 patients with probable AD, positive effects were observed in 36% of patients after six months of treatment (65), a result repeated in a separate study of 115 patients (66). A review of the biological and pharmacokinetic properties, and clinical results of aniracetam treatment in cognitively impaired individuals is available (49). 

In 1981, Chinese Restaurant Asthma was reported following capsule administration of MSG to several asthmatics (37). However, the researchers failed to account for other allergens to which the subjects could have been exposed and did not utilize the scientific practice of a "control" substance which would have helped to determine if glutamate triggered this response. In a double-blind crossover study, chronic asthmatics were challenged with MSG or a placebo. No decrease in pulmonary function was observed (39). 

A clinical trial to evaluate misoprostol as a protector of normal tissue during a course of XRT in cancer patients suggests a reduction in acute normal tissue injury (215). A randomized, prospective, double-blind study indicates that topical misoprostol, administered as an oral rinse 15-20 min before irradiation using conventional 2-Gy (200 rad) fractions, five days a week over 6—7 weeks, significantly protects the oral mucosa from radiomucositis, a frequently observed normal tissue complication during XRT for head and neck cancer (215). 

The activity of ivermectin against the filarial parasite Dirofilaria immitis in dogs suggested a possible role for the control of filarial parasites of humans (20). It has been extensively tested in human onchocerciasis and is now considered to be the dmg of choice. In a single yearly oral dose, it suppresses microfilariae in the skin and eyes and, in most cases, prevents the progression of the disease to blindness. Table 4 shows the results of a 30-patient double-blind study recorded over one year. 

Anistreplase has a considerably longer a half-life than streptokinase, ie, 90 min compared to 20 min (87,88). Moreover, it does not require prolonged infusion to achieve its thrombolytic effects. Anistreplase was found to be highly effective after a single intravenous dose of 30 units over a 5-min period compared to a 60-min infusion of 1.5 million units of streptokinase (89—94). In direct comparative studies, anistreplase was as effective as intracoronary (95,96) and intravenously (96—100) adrninistered streptokinase. In a randomized, double-blind, placebo-controUed study (AIMS trial) with 1004 patients given this modified enzyme, the 30-day mortaUty rate was 12.2% for patients receiving placebo, compared to 6.4% for patients who received 30 units of anistreplase intravenously within six hours of the onset of symptoms (101). 

Pyridoxine is used in morning sickness. Its mechanism of action remains unclear and several reviews of the use of pyridoxine have failed to find conclusive evidence of effectiveness. A recent double blind trial found pyridoxine to be of benefit in reducing nausea only. Some clinicians use pyridoxine as the first drug on the basis that it is the least likely to be toxic to the foetus. 

Wallenborn J, Gelbrich G, Bulst D et al (2006) Prevention of postoperative nausea and vomiting by metoclopramide combined with dexamethasone randomised double blind multicentre trial. Br Med J 333 324-327... 

The clinical trial that resulted in FDA approval of bevacizumab (February 2004) was a randomized, double-blind, phase III study in which bevacizumab was administered in combination with bolus-IFL (irinotecan, 5FU, leucovorin) chemotherapy as first-line therapy for previously untreated metastatic colorectal cancer [3]. Median survival was increased from 15.6 months in the bolus-IFL + placebo arm to 20.3 months in the bolus-IFL + bevacizumab arm. 

Appropriate study design should be selected to achieve the desired outcome. A description of the type/design of frial to be conducted (e.g., double-blind, placebo-controlled, parallel design) and a schematic diagram of trial design. 

Figure 4. Ten bouts of high intensity cycle exercise, each with a duration of 6 sec and with 30 sec rest periods between bouts were performed on a given day. The entire exercise protocol was performed on four separate days by each subject (n = 8), before and after placebo and creatine supplementation. Mean power output was 882 watts. Upper panels (A1 and B1) demonstrate mean revolutions per min during the 0-4 sec period of each bout and the lower panel (A2 and B2) during 4-6 sec of each bout. The left panels (A1 and A2) show results before (o) and after (x) placebo and the right panels (B1 and B2) before (o) and after (x) creatine supplementation. The study was performed in a double blind manner.

Dorus and colleagues (1989) conducted a multicenter, double-blind, placebo-controlled trial in depressed and nondepressed alcoholic veterans. A total of 457 male alcoholic patients, of whom approximately one-third were depressed, were randomly assigned to receive either 600-1,200 mg/day of lithium or a comparable number of placebo capsules. No significant differ-... 

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Efficacy. A pivotal study by Hurt et al. (1997) established the efficacy and safety of bupropion SRfor treatment of nicotine dependence, which led to its approval for this indication by the FDA in 1998. This study was a 7-week, double-blind, placebo-controUed, multicenter trial of three doses of bupropion SR (100 mg/day, 150 mg/day, or 300 mg/day in twice daily dosing). Patients were 6l5 cigarette smokers who smoked at least 15 cigarettes/day. The medication was administered in combination with weekly individual cessation counseling. End-of-trial 7-day point prevalence cessation rates were 19.0% for placebo and 28.8%, 38.6%, and 44.2% for the 100 mg/day, 150 mg/day, and 300 mg/day bupropion doses, respectively. At 1-year follow-up, cessation rates were 12.4% for placebo and 19.6%, 22.9%, and 23.1% for the 100 mg/day,... 

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