Research Frontiers

Johns Hopkins Center of Excellence

Clinical Trials

Mr. Abhi Agarwal is the clinical research coordinator for the BHDC, and his job is to organize the enrollment and participation of patients in various clinical trials run through the Center. As Mr. Agarwal explains, the Center offers a wide range of opportunities for individuals and their families to participate in a variety of clinical research studies. Participation in these research trials is free of charge, thanks to a number of research grants from the National Institutes of Health (NIH), the Huntington's Disease Society of America (HDSA), and the Huntington's Disease Foundation (HDF).

Mr. Agarwal explains that they take a diverse array of approaches to looking at HD, conducting clinical studies that involve genetics, neuropathy, autopsy-based studies, fMRI studies, and basic research studies. He elaborates further on the clinical research studies currently being conducted at the Center:

1) The Longitudinal Core Study: This project is an observational study, which means that it is not intended to test potential treatments for HD, but rather is a study that will help advance our understanding of the natural onset and progression of HD. To enroll in the trial, the only requirement is to have undergone testing for the altered HD gene- participants don't need to actually have HD, because control subjects are needed as well. Any patient that participates in the study at the BHDC is seen annually from their enrollment until their death, and at each yearly meeting they receive full neurological and psychological evaluations to assess the how far along motor, cognitive, and behavioral symptoms have progressed. They also receive functional magnetic resonance imaging, or fMRI scans on every other visit to look for structural differences in the brain over time (changes in the shape of the brain, usually related to nerve cell death), and to compare this to people who do not have HD. Because longitudinal studies often require large numbers of patients, the other goal for this study is to assemble a large database of patients who may be able to simultaneously participate in other clinical trials for HD. The Center has about 90 - 110 participants a year for this study.

Mr. Agrawal emphasizes that for observational longitudinal studies to get results, it takes time to be able to see statistically significant patterns that will further the understanding of HD. But these studies can provide critical information on the disease. For instance, the center has been able to demonstrate using sophisticated brain imaging, that striatal atrophy begins at least 10 years prior to clinical onset, that neuronal cell death correlates best with functional disability, and that the number of trinucleotide repeats in the huntingtin protein has an effect on the rate of HD progression. They found that individuals with the smallest number of trinucleotide repeats appear to have the best prognosis. For more about trinucleotide repeat lengths and the huntingtin protein, click here.

2) Genetic study for Huntington's Disease-like 2 : Researchers at the Baltimore Huntington's Disease Center are also very interested in looking for other genes that cause HD-like diseases. They have actually identified a number of these disorders, which are defined by having very similar symptoms to HD, but do not involve the altered HD gene- the HD gene can be perfectly normal and these symptoms may still appear. One of these diseases is called Huntington's Disease-like 2 (HDL-2) and like HD, it is an adult onset neurodegeneration disorder, it is autosomal dominant, and it is characterized by chorea, cognitive, and psychiatric symptoms. It also involves neurodegeneration and inclusion bodies in the same parts of the brain as in HD. The Center is now working on a project to identify genetic markers for this disease, and to understand what kinds of mutations (other than the altered huntingtin mutation) could cause a disease like HD. They have recently published a paper in 2007, linking HDL2 to a glutamine/CTG repeat mutation on chromosome 16. This kind of mutation is related to, but not the same as the mutation involved in HD. They hope that by understanding the pathology behind HDL-2, it will shed new light on the pathology of HD and other neurodegenerative diseases.

3) Huntington Study Group trials : The BHDC participates in a number of multi-site clinical trials run by the Huntington Study Group. The Huntington Study Group is a non-profit organization composed of physicians, medical researchers and health-care providers from around the world. They have been organizing and conducting clinical trials for HD since 1993. In particular, the Center recruits participants for the observational PHAROS and COHORT studies, the PREDICT-HD study to find neurobiological markers of HD, and the TREND-HD study which is a therapeutic trial for Ethyl-EPA. For more on the Huntington Study Group, please click here, and for information on clinical trials in HD, please click here.

4) Memantine Study : The Center is also conducting a clinical trial with memantine, a drug that has already been approved by the FDA and marketed as Namenda for use in Alzheimer's disease patients. However, not much is known about its use in HD, so the purpose of this clinical trial is to test if it will improve or delay cognitive symptoms of HD. The trial is sponsored by a company named Forest Pharmaceuticals, a company that produces drugs for cardiovascular diseases and CNS diseases like HD. This type of trial is a new indication study, and so it is run as a double-blinded, placebo trial over the course of 6 months. The Baltimore Huntington's Disease Center started recruiting patients for this study in the fall of 2006, and as of March 2007 they have 72 participants. For more information on the use of memantine in HD, click here.

While anywhere from 150-200 people come in for clinical services in an average year, 2006 was an especially busy year for the clinic. Mr. Agrawal also explains that while many people come to the BHDC for genetic testing or patient care, about 25% to 50% of those who come also agree to participate in the clinical trials run through the Center. A good reason for any individual with HD to participate in the Longitudinal Core Study run at the Center is that there will be records of them kept in the Center's database system, and so they can potentially be contacted to be recruited for any new therapeutic clinical trials if they fit the criteria needed to be included in the study.

Last Modified: 11/04/2007

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