BACKGROUND FOR CLINICAL TRIALS: ALZHEIMER’S DISEASE

BACKGROUND FOR CLINICAL TRIALS: ALZHEIMER’S DISEASE

Background

Conducting clinical trials to study Alzheimer’s disease (AD), is quickly becoming a global phenomenon. Some of the challenges include the gathering of biomarkers and identifying neuropsychological deficits. The medical community should pursue standardization of biochemical assays, neuroimaging protocols, and the standardization of critical clinical measures. Any established regulatory requirements for drug/treatment development should leverage cost-effective measures (SCHINDLER, 2010).

Observations & Recommendations

In the development of clinical trial designs for AD treatment, a number of potential target groups exist. Researchers must identify and consider patients from among the 155 mixed causes of dementia. Also, consideration must be given to the disease stage. In patients with mild-to-moderate disease symptoms specific drugs (i.e. immunotherapy) may prove ineffective. Research Clinical Trials (RCTs) with an inclusion of early stage AD patients may provide disease-modifying outcomes, but dissimilar therapeutic windows may exist. Therefore, effective therapeutic strategies are also necessary (Mangialasch et al., 2010).

In terms of drugs selection, compounds with positive outcomes in preclinical and early testing was unsuccessful in large phase 3 RCT’s. One example of a therapeutic agent for AD with costly losses is tramiprostate. Speculation does exist that some RCTs may have been impacted by an incapacity to determine the appropriate therapeutic dosage (i.e. tarenfl urbil), or the correct treatment duration (i.e. lithium, latrepirdine) (Mangialasch et al., 2010).

It’s important to develop multi-faceted measures for RTC’s (cognitive and functional), with realistic desirable outcomes. Biomarkers (i.e. neuroimaging, CSF or blood molecules) that consistently and quantitatively correlate with disease advancement are also recommended. Further, the RTC process should include acquiring baseline data (clinical, biomarkers) useful as resources to interpret future outcomes. Finally for individuals with early AD (i.e. mild cognitive impairment) assessments are advised. This includes both self-rated and observer rated evaluation of activities of daily living (ADL’s) (Mangialasch et al., 2010).

Sample proposed Clinical Trial

A few years ago there was a clinical trial that examined tramiprostate in mild-to-moderate Alzheimer’s disease. The proposed clinical trial would follow the same model. In terms of the materials and methods the use of a double-blinded, placebo-controlled, randomized trial would be recommended. The goal would be to target clinical centers both within the United States and Internationally. The focus would be patients that were aged ≥ 60 years, with mild-to-moderate AD symptoms (Aisen et al., 2011).

Patients would need to have a Mini-Mental State Examination score between 16-26. In the previous study patients were on a consistent dose of cholinesterase inhibitors either with or without memantiine. This same approach would be recommended. The treatment period would be approximately 60 weeks with either placebo, tramiprostate 150 mg or 200 mg BID. There would be an Alzheimer’s disease Assessment Scale (self-rated and observer rated). (CDR-SB) Sum of boxes assessments would be performed every 10 weeks. There would be a baseline and 60 week magnetic resonance imaging (MRI). The measurement of hippocampus volume (HV) would be considered although not necessarily used (Aisen et al., 2011). Early detection ensures that greater than 35 percent of people with AD will have an early diagnosis in their medical records. This is especially important for African-Americans, Hispanics, and other diverse groups with disproportionate rates of AD (alz.org, 2015).

References

Aisen, P. S., Gauthier, S., Ferris, S. H., Saumier, D., Haine, D., Garceau, D., Duong, A., Suhy, J., Oh, J., Lau, W. C., & Sampalis, J. (2011, February). Tramiprosate in mild-to-moderate Alzheimer’s disease – a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Archives of Medical Science, 7(1), 102-111.

Mangialasch, F., Solomon, A., Winblad, B., Mecocci, P., & Kivipelto, M. (2010, July). Alzheimer’s disease: clinical trials and drug development. ProQuest, 9(7), 702-716.

SCHINDLER, R. J. (2010, November 4). STUDY DESIGN CONSIDERATIONS: CONDUCTING GLOBAL CLINICAL TRIALS IN EARLY ALZHEIMER’S DISEASE. The Journal of Nutrition, Health, and Aging, 14(4), 312-314.

alz.org. (2015). early detection of alzheimer’s disease: important information for physicians. Retrieved from http://www.alz.org/mnnd/documents/10signs_PhysicanFactSheet_final.pdf