H2 Histamine Receptor Blockade in the Treatment of Alzheimer Disease: A Randomized, Double-Blind, Placebo-Controlled Trial of Nizatidine.

Carlson MC, Tschanz JT, Norton MC, et al.

Nizatidine Use in Alzheimer Disease The use of over-the-counter dosages of histamine H2-receptor antagonists (H2RAs) has been proposed in some studies as a way to delay or prevent the onset of Alzheimer Disease (AD). No known current studies to test efficacy of H2RAs are underway, but this study was conducted to test whether nizatidine, an H2RA, can delay the progression of dementia in established AD. Method Fifty-one older (range 67-96) men and women with AD were recruited from the Cache County Study on Memory in Aging to participate in a one-year, randomized, double-blind, placebo-controlled trial. Patients were stratified by age and by the presence of one or more ε4 alleles at the APOE locus, and randomized to receive either nizatidine 75 mg twice daily or a matching placebo. Intention-to-treat analyses were conducted for baseline, and at the sixth and twelfth months. The two groups (nizatidine and placebo) were compared using the 12-month difference scores and repeated measures analyses of variance (ANOVA). Results Five subjects died, but a central adjudication committee determined that trial medication was not responsible. Study participants showed significant declines in language, fluency, and praxis, but most measures of memory had already bottomed-out. Compliance was an issue in both groups, but repeated analyses showed no significant difference. Overall, no consistent and significant benefit in any tested cognitive domain was associated with the use of nizatidine. The placebo group also contained three highly educated persons; however, repeated studies determined this factor had no effect on outcome. Discussion This randomized, controlled trial in AD patients showed no significant effect of nizatidine on the progression of cognitive decline in AD. Therefore, there is no evidence to support the use of H2RAs in treatment of established Alzheimer dementia. The researchers note that it's possible that some interventions that can delay onset do not affect the progression of cognitive symptoms after the diagnosis of AD. Limitations of the study include sample size; the difference in education level, which could be stratified in future trials to increase utility; and the choice of drug. Alzheimer Dis Assoc Disord 2002 Jan-Mar;16(1):24-30. Copyright © 2002 and published by Medical Economics Company at Montvale, NJ 07645-1742. All rights reserved. Return to Top