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Clinical Trials on Huntington’s disease

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.

For more information on the different phases of clinical trials, click here.

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^

(as of October 2017)


SIGNAL is a Phase II trial that studies the safety, tolerability, and effectiveness of VX15, an antibody that aims to slow the impairments in cognition, movement and behavior in HD. VX15 is designed to deactivate a specific protein, semaphorin 4D (SEMA4D), that guides the activation and movement of cells. SEMA4D may be responsible for the inflammation that occurs in the brains of those with HD. Previous research suggests that VX15 may be able to block SEMA4D, reducing brain inflammation and slowing negative side effects. SIGNAL is a multi-center, randomized, double-blind placebo study at 20 sites in the US. They are seeking 116 people, ages 21 or older, who are either early in the progression of the disease or at risk for the disease. (For the most up to date information about SIGNAL, click here.)

Ongoing Studies that are No Longer Enrolling Participants^

(as of October 2017)


First-HD and ARC-HD are Phase III clinical trials investigating the efficacy and safety of deutetrabenazine (SD-809) on HD patients who present with chorea. Deutetrabenazine has the same mechanism of action as the current treatment for chorea, tetrabenazine, however it is broken down much more slowly. The hope is that this slow release will allow the drug to deliver the same relief as tetrabenazine, with a lower daily dose and fewer side effects. The most common adverse side effects reported thus far, affecting ≥5% of participants, have been drowsiness, dry mouth, diarrhea, insomnia, and fatigue, though all these effects have been reported with tetrabenazine as well. While First-HD will establish the safety and effectiveness of deutetrabenazine, ARC-HD focuses on how switching to deutetrabenazine affects patients currently taking tetrabenazine to treat chorea. First-HD will last up to 4 months and ARC-HD will last up to 14 months. These studies are no longer enrolling participants. (For the most up to date information on these studies, click here).


LEGATO-HD is a Phase II clinical trial to investigate the efficacy and safety of laquinimod in the treatment of HD. Laquinimod is thought to decrease inflammatory responses that occur in the brain of HD patients. The primary metric for this study is change from baseline in the Unified Huntington’s Disease Rating Scale – Total Motor Score (UHDRS-TMS) after 12 months of treatment with varying doses of laquinimod. Information regarding safety and side effects is also being collected. This study is sponsored by Teva Pharmaceuticals in collaboration with the Huntington Study Group (HSG) and European Huntington’s Disease Network (EHDN). This study is no longer enrolling participants. (For the most updated information on this study, click here).


PRIDE-HD is a Phase II randomized, double-blind clinical research study of the efficacy and safety of the  drug pridopidine. Pridopidine is a dopamine stabilizer that can enhance or inhibit dopamine-controlled functions.  For more information on the role dopamine plays in HD, click here. This study is investigating the effect pridopidine has on movement, thinking, and behavior in individuals with HD after 26 weeks of receiving the drug or placebo. This study is sponsored by Teva Pharmaceuticals in collaboration with Huntington Study Group (HSG) and European Huntington’s Disease Network (EHDN). 400 participants have been enrolled globally across 51 study sites. This study is no longer enrolling participants. (For the most up to date information on this study, click here).

Recently Completed Clinical Trials^

(as of October 2017)


2CARE was a Phase III trial that aimed to study coenzyme Q10 as a potential treatment for HD. For more on coenzyme Q10, click here. The study aimed to measure the effectiveness of coenzyme Q10 in slowing the symptoms of HD and to study the long-term safety of administering the compound to HD patients. Previous studies have shown that coenzyme Q10 slightly slowed the progression of HD, but not enough to yield significant results. Compared to these previous studies, 2CARE used a much higher dosage for a longer time period. To date, it is the largest therapeutic clinical trial of HD, with enrollment of over 600 in the United States, Canada, and Australia. The study began in March of 2008 and was completed in July 2014. 2CARE was a double blind placebo study, in which participants were randomly assigned to one of two groups. The experimental treatment group received oral administration of coenzyme q10 in chewable form twice a day, for a total of 2400 mg/day. Researchers compared total functional capacity (TFC) scores, tolerability, adverse events, vital signs, and laboratory test results between the two groups. Results found that there were no statistically significant differences between treatment groups, leading the researchers to conclude that coenzyme Q10 is not a justified treatment option to slow functional decline in HD. (For more information on the results of 2CARE, click here.)


Creatine, Safety, Tolerability, & Efficacy in Huntington’s disease (CREST-E), conducted by The Huntington Study Group (HSG), Massachusetts General Hospital, and the University of Rochester, was a Phase III clinical trial that aimed 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 HD-model mice supplemented with creatine displayed improved motor performance, diminished loss of brain mass, reduced huntingtin aggregates, and delayed neuronal death. Participants in CREST-E were randomly selected to receive either 40g per day of powdered creatine monohydrate or 40g per day of a placebo. The study was a large clinical trial, involving 46 research centers from around the world and enrolling around 550 participants. The study lasted 48 months and was completed in December of 2013. The results did not show statistically significant differences between the treatment and placebo groups. This study provided evidence that creatine is not beneficial for slowing functional decline in patients with early symptomatic HD. (For the most up to date information on this study, 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. Minocycline is an antibiotic that is primarily used to treat acne and other skin disorders. For more on minocycline, click here.  The study is a Phase II clinical trial that was started in 2006 and completed in November 2008 by the Huntington Study Group (HSG) with funding by the FDA Office of Orphan Products Development. It was a double-blind 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 was abandoned. (For more about the results of the DOMINO study, click here.)


Pridopidine (ACR16), as described in the Pride-HD clinical study, is a dopamine stabilizer that can enhance or inhibit dopamine controlled functions. For more information on the role dopamine plays in HD, click here. The Huntington Study Group (HSG) conducted a Phase II clinical trial testing different doses of pridopidine on HD patients age 30 and older. HART was sponsored by NeuroSearch Sweden AB and was conducted in 27 research sites across North America. Previous studies showed that pridopidine 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 were randomly assigned to one of four groups: three experimental groups given different doses of pridopidine and a placebo group. The study occurred over the course of 12 weeks and was completed in May 2010. While there was no statistically significant treatment effect, the overall results suggest that pridopidine may be beneficial in improving motor function because patients in the highest dosage group (90 mg/day) displayed significant improvement in motor function as measured by the modified Motor Score (mMS). (For more on the HART study, click here.)


HORIZON was a Phase III clinical trial conducted by the Huntington Study Group 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 neurons 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 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. The study was ended early in April 2011 when the researchers discovered there were no statistically significant differences 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. (For more on the HORIZON study, click here.)


Early in 2009, the Huntington Study Group (HSG) received funding from the NIH to test the safety and tolerability of coenzyme-Q10 and remacemide hydrochloride in individuals who have tested positive for HD but do not yet show any motor symptoms. The study was called PREQUEL (Study in PRE-manifest Huntington’s disease of coenzyme Q10 (UbiquinonE) Leading to preventive trials) and was a Phase II trial. The study was conducted at 23 clinical sites throughout the United States and was the first therapeutic research study in pre-manifest HD patients. Participants were randomly assigned to experimental groups receiving 600, 1200, and 2400 mg/day of coenzyme q10. At each dose, neither remacemide nor coenzyme Q10 produced significant slowing in functional decline in early HD. (For more on the PREQUEL study, click here.)


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),  an omega-3 fatty acid commonly found in fish oil, slowed the progression of motor decline in HD patients. 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. This lack of improvement in both groups at 6 months yet improvement by 12 months of treatment could be explained by detection or attrition bias or chance but could also indicate that ethyl-EPA treatment may improve motor features in patients with HD over a longer treatment course. 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. (For more on the TREND-HD study, click here.)


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 on the TETRA-HD study, click here.)

For more information:^


-L. Slang, 10-16-17