What are clinical trials?
In order for any drug or treatment to be approved for human use by the FDA, it must first successfully pass clinical trials. A clinical trial is a medical or health-related research study in humans that follows a strict protocol in a carefully monitored, scientifically controlled setting. Clinical trials are generally conducted after a drug or treatment has shown promise in research studies using animal models.
What are the different types of clinical trials?^
There are four main types of clinical trials: treatment trials, prevention trials, diagnostic trials, and screening trials.
- Treatment trials test the effects of new drugs, new combinations of drugs, or new procedures used to treat an illness or condition. Participants in this type of trial would already experience symptoms of HD and could be in any stage of HD.
- Prevention trials aim to prevent or delay onset of a disease in people who are at risk and test the effects of treatments that do so. Participants in this type of trial would be pre-symptomatic HD patients, usually people who have tested positive for the HD gene but have not yet exhibited any symptoms.
- Diagnostic trials are conducted to discover better procedures to diagnose an illness or disease.
- Screening trials are conducted to discover better ways to detect an illness or disease.
Diagnostic and screening trials are not needed to diagnose HD since current genetic tests can reliably and accurately identify HD. However, these types of trial design may be useful to research presymptomatic measures of HD disease progression and/or develop ways to better assess disease risk in the intermediate range where definitive genetic diagnosis is not currently possible. For more on genetic testing of HD, click here.
Clinical trials are conducted in phases.
- In Phase I trials, researchers first test a new treatment on a small group of individuals, typically 20-80 people, to evaluate its safety, determine a safe dosage range, and to identify side effects.
- Once the treatment passes Phase I trials, Phase II trials are conducted on more people, around 100-300 people, to see if it is effective and to further evaluate its safety and side effects.
- Once Phase II trials are completed successfully, the drug moves onto Phase III trials, in which researchers confirm the drug’s effectiveness, monitor any side effects, compare it to standard treatments, and collect information that will allow the experimental drug or treatment to be used safely long-term.
- Only after the drug or treatment has passed all phases will it be approved by the government.
All clinical trials have criteria specifying who can or cannot participate. There are many risks and benefits to participating in a clinical trial. For example, participants contribute to medical research, have access to medical care, and if assigned to the treatment group, are given new potential treatments throughout the trial. However, participants may also experience negative side effects as a result of participating, or they may receive a placebo. Clinical trials must follow strict ethical codes and are highly regulated to ensure the safety of participants as much as possible.
What is the Huntington Study Group?^
The Huntington Study Group (HSG) is an international non-profit group whose aim is to support clinical research of Huntington’s disease (HD). It was formed in 1993 and has members and research sites in the US, Canada, Europe, Australia, New Zealand and South America. The HSG often partners with pharmaceutical companies, private foundations, and government agencies to fund research investigating the effects and safety of HD interventions. (For more information on the HSG, click here).
Ongoing Studies that are Currently Enrolling Participants^
2CARE is a phase III trial that aims to study coenzyme-Q10 as a potential treatment for HD. For more on coenzyme-q10, click here. The study aims to measure the effectiveness of coenzyme q-10 in slowing the symptoms of HD and to study the long-term safety of administering the compound to people with HD. Previous studies have shown that coenzyme q-10 slightly slowed the progression of HD, but not enough to yield significant results. Compared to these previous studies, 2CARE uses a much higher dosage for a longer time period. To date, it will be the largest therapeutic clinical trial of HD, with expected enrollment of over 600 in the United States, Canada, and Australia. The study began in March of 2008 and is expected to be completed by April 2014. 2CARE is a double blind placebo study, in which participants are randomly assigned to one of two groups. The experimental treatment group will receive oral administration of coenzyme q10 in chewable form twice a day, for a total of 2400 mg/day. In a preliminary study called Pre2CARE, dosages ranging from 1200 to 3600 mg/day were tested; 2400 mg/day appeared to be the most effective dosage, as smaller dosages were not as effective, and larger dosages resulted in the mildly unpleasant side effect of upset stomach. Researchers will compare total function capacity (TFC) scores, tolerability, adverse events, vital signs, and laboratory test results between the two groups.
The Huntington Study Group (HSG), Massachusetts General Hospital, and the University of Rochester are currently conducting a phase III clinical trial to assess the effects of creatine supplements on slowing the progression of symptoms in HD patients. Creatine is a molecule naturally produced in the body and consumed in the diet, found mostly in meat. Previous studies conducted on transgenic mouse models have shown that mice supplemented with creatine displayed improved motor performance, diminished loss of brain mass, reduced huntingtin aggregates, and delayed neuronal death. The study is called the Creatine, Safety, Tolerability, & Efficacy in Huntington’s disease (CREST-E). Participants are randomly selected to receive either 40g per day of powdered creatine monohydrate or 40g per day of a placebo. The study is a fairly large clinical trial. It will involve 44 research centers from around the world and enroll up to 650 participants. The study will last 37 months and is estimated to be completed in December of 2014. (For the most updated information on this study, click here).
Earlier in 2009, the HSG received funding from the NIH to test the safety and tolerability of coenzyme-Q10 in individuals who have tested positive for HD but do not yet show any motor symptoms. The study is called PREQUEL (Study in PRE-manifest Huntington’s disease of coenzyme Q10 (UbiquinonE) Leading to preventive trials) and is a phase II trial. The study will be conducted at 10 clinical sites throughout the nation and is the first therapeutic research study in pre-manifest HD patients. Participants will be randomly assigned to experimental groups receiving 600, 1200, and 2400 mg/day of coenzyme q10. The principal investigators hope that this initial trial will lead to later trials that study the delay of HD.
Ongoing Studies that are No Longer Enrolling Participants^
ACR16 is a dopamine stabilizer and can enhance or inhibit dopamine controlled functions. For more information on the role dopamine plays in HD, click here. The HSG is conducting a phase II clinical trial testing different doses of ACR16 on HD patients age 30 and older. HART is sponsored by NeuroSearch Sweden AB, a biopharmaceutical company, and is being conducted in 35 research sites across North America. Previous studies showed that ACR16 is safe and tolerable in patients with HD and Parkinson’s disease. Additionally, it has been shown to significantly improve patients’ voluntary and involuntary movements. Participants are randomly assigned to one of four groups-three experimental groups given different doses of ACR16 and a placebo group. The study occurs over a course of 12 weeks. As of October 2010, results have been promising, as patients in the highest dosage group (90 mg/day) displayed significant improvement in motor function as measured by the modified Motor Score (mMS).
Recently Completed Clinical Trials^
HORIZON was a phase III clinical trial conducted by the HSG and the European Huntington’s Disease Network that investigated whether dimebon is safe and effective in improving cognitive abilities in patients with HD. Dimebon is an experimental drug that has been shown to prevent the death of brain cells in animal models and is currently being tested to treat HD and Alzheimer’s Disease. It is thought to work by stabilizing and improving function of the mitochondria. For more information on dimebon, click here. The study was conducted in various centers in the United States, Canada, Europe, and Australia. It was a double-blind, placebo study in which participants were either given 60 mg of Dimebon daily or a placebo. Results showed that dimebon is not effective in treating HD. There was no statistically significant difference in symptoms between the experimental and placebo groups. According to the president and chief executive officer of Medivation, development of dimebon in HD will be discontinued.
Minocycline is an antibiotic that is primarily used to treat acne and other skin disorders. For more on minocycline, click here. The goal of DOMINO was to assess whether minocycline was safe and effective in slowing HD progression and whether further studies should be conducted. The study is a phase II clinical trial that was started in 2006 and completed in November 2008 by the HSG with funding by the FDA Office of Orphan Products Development. It was a double-blind, placebo experiment in which participants were randomly assigned to a treatment group that received 100mg of minocycline twice daily or a placebo. The TFC scores of the two groups were then compared. Results showed that while minocycline was safely tolerated, it did not produce a significant effect in terms of delaying HD symptoms, and thus, further study of minocycline in treating HD is not warranted.
TREND-HD was a large phase III trial that began in September 2005 and was completed in August 2007. The goal of the study was to determine whether ethyl-EPA (Miraxion) slowed the progression of motor decline in HD patients. Ethyl-EPA is an omega-3 fatty acid commonly found in fish oil. Study participants had mild to moderate HD, meaning they displayed early signs of HD but were self-sufficient in daily living activities. For the first 6 months, the treatment group received ethyl-EPA while the placebo group received a placebo. For the next 6 months of the study, the placebo group was also given the active drug. Interestingly, there were no significant differences in Total Motor Scores between the two groups after the first 6 months of the placebo study. However, after the next 6 months in which all participants received the drug, the experimental group showed improvement as compared to the group that had initially received the placebo for the first 6 months. Further studies will need to be conducted to determine the efficacy of ethyl-EPA. There did not appear to be any safety concerns. After the study was completed, the investigators and sponsor of the study, Amarin Neuroscience Ltd., took the unprecedented step of telling the study participants about the results of the study by calling them and inviting them to a telephone conference regarding the study results. Study participants are typically not informed of the results of the clinical trials they participated in.
Huntington Study Group (HSG) and Prestwick Pharmaceuticals collaborated on a clinical trial. Called TETRA-HD involving tetrabenazine, a dopamine depletor. Led by Dr. Frederick J. Marshall from the University of Rochester Medical Center, TETRA-HD was a phase III clinical trial with the goal of determining the optimal dosage of tetrabenazine in treating chorea in people with HD. The trial was carried out at 16 different HSG sites in the United States, involving a total of 84 participants with HD. Fifty-four of the participants were randomly assigned to receive tetrabenazine for 12 weeks with increasing dosages over the first 7 weeks. The other 30 served as the comparison group and received a placebo. The results of the study indicated that tetrabenazine is effective in treating chorea with side effects that are less severe than those associated with other anti-choreic drugs. On the CGI Global Improvement Scale, 6.9% of the patients receiving placebo had more than minimal improvement compared to 45.1% of the patients receiving tetrabenazine. Clinical assessments showed that tetrabenazine was associated with drowsiness and insomnia in four patients, depressed mood in two, parkinsonism in two and akathisia in two. Most cases of adverse effects improved after adjusting dosage levels, but the risk of side effects should be considered. These results confirm the benefits of tetrabenazine usage in ameliorating the symptoms of chorea. In August 2008, the FDA approved tetrabenazine as the first drug for treatment of chorea, and it is used worldwide today.
For more information:^
-A. Zhang, 7-5-11