Clinical trial, double blind

There are data from several small clinical trials with A9-THC or with nabi-lone (25), a synthetic cannabinoid agonist. The first trial (double blind, placebo-controlled) was by Petro and Ellenberger who recorded that in a group of nine patients, administered up to 10 mg A9-THC, three felt that they were better able to walk [136], The authors measured deep tendon reflexes, muscular resistance to stretch of the legs and abnormal reflexes, and found improvements. 

Selection criteria Original articles, English, clinically relevant, adult or pediatric humans randomized controlled trials, double blinded... 

B. Benzomorphans - Clinical trials of the d 1 isomers of pentazocine (k) have shown "16 th both analgesic activity and side effects reside in the levo-isomer. Other trials, double-blind in many patients, confirm" 7,18 the activity of the compound at about one-third that of morphine, while measurements of respiratory depression in treated patients suggest" 9,20 this to be less than morphine at equianalgesic doses. The oral absorption has been determined2 1 and metabolic breakdown found22 to occur predominantly at the terminal methyl groups of the side chain. Reports of addiction to the injected form of pentazocine have been published ,24,25 including one to the oral form. 

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). 

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 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. 

Szeimies RM, Gerritsen MJ, Gupta G, Ortonne JP, Serresi S, Bichel J, Lee JH, Fox TL, Alomar A (2004) Imiquimod 5% cream for the treatment of actinic keratosis results from a phase III, randomized, double-blind, vehicle-controlled, clinical trial with histology. J Am Acad Dermatol 51 547-555... 

Haddad AL, Matos LF, Brunstein F, et al (2003) A clinical, prospective, randomized, double-blind trial comparing skin whitening complex with hydroqui-none vs. placebo in the treatment of melasma. Int J Dermatol 42 153-156... 

Breneman DL, Stewart D, Hevia O, Hino PD, Drake LA (1998) A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1% cream to vehicle in patients with rosacea. Cutis 61 44-47... 

Tollefson GD, Sanger TM (1997). Negative symptoms a path analytic approach to a double blind, placebo controlled clinical trial with olanzapine. Am J Psychiatry 154,... 

FIGURE 5.2 Clinical outcome of patients in the double-blind, proof-of-concept trial evaluating EPO in acute stroke, (a) Barthel Index (rhEPO vs. placebo, p < 0.05). (b) Modified Rankin Scale (rhEPO vs. placebo, p < 0.07) on day 30. Dead patients received the worst possible score. Evolution of lesion size of patients in the efficacy trial of Albumin in acute stroke, ((a-1) and DWI and (a-2) FLAIR.) (Reprinted with permission from reference 50.)... 

Yamaguchi T, Sano K, Takakura K, Saito I, Shinohara Y, Asano T, Yasuhara H. Ebselen in acute ischemic stroke a placebo-controlled, double-blind clinical trial. Ebselen study group. Stroke 1998 29 12-17. 

The first proper double blind trial of embryonic implants in 40 PD patients (20 undergoing just surgery without any implant), has shown no improvement in patients over 60 years but some clinical benefit (fewer symptoms between levodopa dosing) in those below that age. Unfortunately some of these responders eventually developed dyskinesias, a sign of too much dopamine, and further implants were halted until the technique has been re-evaluated, see Freed, CR et al. N EnglJ Med 2001, 344 710-719. 

The mean dietary intake of soy isoflavones in Asian populations consuming soy-based diets ranges from 20-40 mg isoflavones/day, with upper percentile consumer intakes of 70 mg/day (corresponding to around 1 mg/kg body weight). In the six month intervention studies in Western postmenopausal women, the effective dose for improved BMD was around 80-90 mg/day, while in the one year, randomized, double-blind, placebo controlled clinical trial, the effective dose was 54 mg/day. Overall, the dietary recommendation is to consume 50 mg isoflavones/day in combination with standard nutritional requirements for calcium and vitamin D. 

KLIPPEL K F, HiLTL D M, scHipp B (1997) A multicentric placebo controlled double-blind clinical trial of beta-sitosterol for the treatment of benign prostate hyperplacia. British J Urology, 80(3) 427-32. 

Clemens, J.A., Bulkley, G.B., Cameron, J.L., Milligan, F.L., Hutcheon, L., Horn, S.D. and MacGowan, S.W. (1991). Effect of xanthine oxidase inhibition with allopurinol on the incidence and severity of post-ERCP pancreatitis and hyper-amylasaemia in a prospective, randomized, double-blind, placebo-controlled clinical trial of 168 patients. Gastroenterology 100, A270. 

Jiang, R. H., Shu, L., Zhang, H. Y. et al. (2006). A phase II randomized double blind multi-centers and parallel control clinical trial for bupropion SR in the treatment of depressive disorders. Chinese Journal of New Drugs, 15(2), 128-31. 

Wu, D., Xiung, X., Wang, L. et al. (2003). A double-blind comparison trial of 1-stepholidine and perphenazine in treatment of schizophrenia. Chinese Journal of New Drugs and Clinical Remedies, 22(3), 155-60. 

Zhang, Z., Wang, X., Chen, Q. etal. (2002). Clinical efficacy and safety ofhuperzine Ain treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial. National Medical Journal of China, 82( 14), 941-5. 

Unfortunately, not all products that are used in clinical trials are available in the United States. In a randomized, double-blind, multicenter European study, 1069 men with moderate benign prostatic hyperplasia were randomized to receive saw palmetto (Permixon" )1 160 mg twice daily (90% free and 7% esterified fatty acids) or finasteride 5 mg once daily for 6 months [32]. As determined by patients and physicians, Permixon offered similar improvement in symptoms related to benign prostatic hyperplasia compared to finasteride. Since Permixon is not available in the United States, it should be recommended to patients to use a product that is similar to Permixon that contains a standardized extract of saw palmetto containing 85-95% sterols and fatty acids [18]. 

Why are side effects important Imagine that you have been recruited for a clinical trial of an antidepressant medication. As part of the required informed-consent procedure, you are told that you may be given a placebo instead of the active medication, but because this is a double-blind trial, you will not be told which you are getting until the study is over. You are told that... 

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