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LEADING THE FEDERAL EFFORT ON AGING RESEARCH

Putting Treatment Hypotheses to the Test in Clinical Trials


man and womanPrevious sections of this report have described some of NIH’s ongoing pilot and full-scale AD clinical trials that are testing exercise, diet, and chronic disease intervention strategies (see "Lessons Learned from Couch Mice, Marathon Mice, and Men and Women Who Like to Walk", "A Healthy Diet May Be Important to Brain Health as Well as Body Health", and "Managing Chronic Illness: A Possible Preventive Strategy for AD?"). This section describes other treat-ment clinical trials, most of which are testing drugs for their effects on AD progression or on behavioral symptoms.

Pilot MCI and AD Treatment Trials

Before beginning a full-scale clinical trial, investigators often conduct pilot clinical trials. The data gathered in these trials help scientists determine which interventions should go on to the next step. Here are a few of the current pilot clinical trials in MCI and AD:

  • Nicotine skin patch and amnestic MCI. Some of the 60 non-smoking participants in this study are being given a nicotine patch and others a placebo patch. Nicotine imitates many of the actions of acetylcholine. Preliminary studies have suggested that short-term administration of nicotine appears to improve memory in patients with mild memory loss and early AD. Furthermore, nicotine administration appears to have significant neuroprotective effects, and it may have positive influences on APP processing. The primary goal of this pilot trial is to demonstrate whether the nicotine patch is safe to administer over a 1-year period to the participants with amnestic MCI. Study investigators also hope to determine whether nicotine can reduce memory loss and improve other cognitive symptoms over the longer term and whether it can help delay the progression of cognitive impairment and development of AD.
  • Raloxifene and women with AD. This 12-month pilot trial will examine the effects of the osteoporosis drug, raloxifene, on cognitive function, ability to carry out daily activities, and biomarkers in older women with AD. In animal studies, raloxifene affects neuronal activity in ways that might be expected to improve cognitive function, and recent clinical data support the idea that this drug could lessen dementia symptoms in women with AD.

Full-scale AD Treatment Clinical Trials

At the time of this report, the NIH is supporting more than 30 clinical trials of treatments for people with AD. Many of these are part of the Alzheimer’s Disease Cooperative Study. Here are highlights of a few of these trials.

  • Divalproex sodium and agitation. A previous ADCS clinical trial of divalproex sodium (Valproate), conducted in 150 nursing home residents, was designed to see whether the medication could ease agitation in people with severe AD. In contrast to other trials, results from this multi-center trial did not show that divalproex sodium was helpful for people with severe AD. A trial currently underway is examining whether valproate therapy can delay or prevent agitation and psychosis in people with mild to moderate AD. Enrollment is nearly complete, with close to 300 people already participating. Researchers also are interested in seeing whether its possible neuroprotective properties have any effect on slowing the rate of cognitive decline.
  • Huperzine A and cognitive function. This ADCS trial is evaluating whether huperzine A, a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata, can slow the progression of cognitive decline in people with mild to moderate AD. A number of small, randomized controlled trials in China have indicated that people with AD who were treated with huperzine A performed better on memory tests than those on placebo. Investigators also are interested in huperzine A because it has antioxidant and neuroprotective properties that suggest it may be useful in treating AD. The study, which has enrolled 140 of the 150 participants, is taking place in about 28 sites nationwide, and recruitment is ongoing. Participants are being randomly assigned to three equal groups—two groups will receive varying amounts of huperzine A every day and the third group will receive a placebo.
  • Growth hormones and MCI. Some data suggest that a particular set of growth hormones that work together has a significant beneficial effect on memory and reasoning ability. This hormonal group—growth hormone releasing hormone/growth hormone/insulin-like growth factor 1 (GHRH)—is also called the somatotrophic hormonal axis. This clinical trial is determining whether GHRH is beneficial for individuals with amnestic MCI. Investigators will examine the effects of GHRH on the cognitive function of 80 healthy older adults and 80 older adults with amnestic MCI.
  • Depression in AD. Major depression affects approximately 25 percent of people who have AD, so finding effective ways to treat this condition is an important priority for AD research. In fact, depression in AD is increasingly recognized as a condition separate from major depression. NIMH-funded researchers at Johns Hopkins University have developed and published criteria for health care providers to use in diagnosing depression of Alzheimer’s disease (dAD) (Rosenberg et al., 2005). These criteria are broader than those used to diagnose major depression, and importantly, were developed with the help of AD caregivers. The researchers are conducting a clinical trial of dAD treatment and will validate the new diagnostic criteria as part of the trial. They have completed one clinical trial of the antidepressant medication sertraline (Zoloft) to examine the effects of antidepressant treatment on cognition and daily functioning, as well as on caregiver burden (Munro et al., 2004). Overall, results from the cognitive measures for the trial’s 44 participants indicate that neither improved mood nor use of sertraline was associated with cognitive changes over time in the participants. Further exploration of the data suggested that the cognitive abilities of women treated with sertraline improved, compared to women who did not receive treatment. In contrast, the cognitive abilities of men taking sertraline worsened compared to those not treated.
  • Atypical antipsychotics to treat psychosis in AD. NIMH-funded investigators at the University of Southern California Keck School of Medicine recently published results from a clinical trial called the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) (Schneider et al., 2006). This trial was designed to assess the effectiveness of atypical antipsychotic drugs for use in people with AD who experience hallucinations, delusions, agitation, or aggression. These symptoms are common in people with AD, and they can be very distressing to caregivers. The results from the trial showed no significant differences between the antipsychotic medications or placebo. Thus, the findings suggest a lack of significant clinical benefit of treatment with atypical antipsychotic medications in AD.

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Page last updated Nov 25, 2008

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