HD research news - medical research into treatment & prevention

CARE-HD study results - questions and answers

March 2002

Background

What was the CARE-HD study about?

CARE-HD was a randomized, double-blind, controlled clinical trial of remacemide and co-enzyme Q10 (CoQ10). The study was conducted by the Huntington’s Study Group (HSG) at 37 sites throughout the United States and Canada.

CARE-HD was funded by the National Institute of Neurologic Disease and Stroke (NINDS), which is a branch of the National Institutes of Health in the United States. The study also received support from AstraZeneca (the maker of the drug remacemide), and Vitaline Corporation (American producer and distributor of CoQ10).

What is remacemide, and why was it tested?

Remacemide is a new drug made by AstraZeneca that can block the neurotransmitter, glutamate, in the brain that has long been suspected of contributing to the death of brain cells in Huntington’s disease. Its use in the CARE-HD study was purely experimental.

What is co-enzyme Q10, and why was it tested?

Co-enzyme Q10 (CoQ10) is an anti-oxidant, and plays a role in the function of mitochondria, the energy factories of human cells. Animal and human research has suggested that a reduced supply of cellular energy and/or tissue oxidation, may play a role in the nerve cell death that occurs in HD.

Who was tested as a part of the study?

CARE-HD was a 30-month study, involving 347 people in the early stages of HD. Testing was not conducted with participants at other stages of Huntington’s disease.

How was the study done?

Participants in the CARE-HD study were assigned to one of four different treatments:

• 25% received remacemide;
• 25% received CoQ10;
• 25% received a combination of remacemide AND CoQ10;
• 25% received a placebo (no medication of any kind).

Each participant was monitored over the 30-month study period using standardized functional, neurological, and neuropsychological tests. A smaller number of participants also underwent brain scans (using MRI). Study investigators, using all of these testing techniques, were looking to find some kind of impact on each participant’s Total Functional Capacity (TFC). The TFC is a standardized scale used to express the effect of HD on an individual as a number or grade. A person rated at 13 is said to be normal. A person rated at 0, or the low end of the scale, would be someone who is severely disabled.

At the beginning of the trial, the average TFC rating for the 347 study participants was approximately 10. Ultimately, the purpose of CARE-HD was to discover whether a person taking remacemide, CoQ10, or a combination of the two would experience a slower decline on the TFC scale compared to someone who was not taking any medication (the placebo).

Results: Remacemide

What do the study results say about remacemide?

Participants who were given remacemide, at 200 mg three times a day for 30 months, experienced the same rate of decline on the TFC scale as the study participants who were given a placebo (no medication).

In short, remacemide was shown to have no benefit for persons in the early stages of Huntington’s disease.

Remacemide is an investigational drug that is not approved by the Food and Drug Administration. Because the CARE-HD study did not demonstrate that remacemide was of benefit to persons in the early stages of Huntington’s disease, the drug is no longer available for individuals with HD.

Results: CoQ10

What do the study results say about CoQ10?

Treatment with co-enzyme Q10 (CoQ10) involved participants taking 300 mg twice a day, with food. In this study, CoQ10 was supplied in chewable wafers provided by Vitaline Corporation in the United States. Over the 30-month study period, no statistically significant decrease in the rate of decline of Total Functional Capacity (TFC) was observed.

More specifically, very small decreases in the rate of decline on the TFC scale ( 13%), as well as the HD Independence Scale (17%) were detected. However, establishing that the beneficial effects registering in the range between 13-20% are not due to chance, requires a study with many more patients than were actually used in CARE-HD.

Consequently, the CARE-HD investigators, the Huntington’s’s Disease Society of America (HDSA), the Huntington’s Society of Canada (HSC) and the Hereditary Disease Foundation agree that the CARE-HD results about CoQ10 are inconclusive, but do not indicate that HD should be treated with CoQ10.

In short, there is no definite evidence that any true benefit will result from a person in the early stages of HD taking CoQ10 as it was prescribed in this study.

I know the study results say there is little chance that CoQ10 can have a positive benefit to me, but if I chose to take it anyway, how would I go about it?

There is no definite evidence that any benefit will result from a person in the early stages of HD taking CoQ10 as it was prescribed in this study. In addition, the results of the CARE-HD study cannot be applied to persons who are at risk for HD, presymptomatic, or in the intermediate or advanced stages of HD.

The decision to take CoQ10, despite the study results, should be done in consultation with a physician. CoQ10 is a nutritional supplement that is available in pharmacies and health food stores. The formulations of CoQ10 may differ chemically, affecting their activity and ability to be absorbed. Also, different additives may be present in many of the formulations of CoQ10. The effects of some of the additives in various preparations of CoQ10 are not known - there is no information about how these differences might affect a person with Huntington’s disease.

Other Details

Will there be more information made available about the study?

After August 14, 2001, the statistical detail concerning the study results will be published and made available to the public. The Huntington’s Study Group is hoping to conduct follow-up studies to better establish whether or not CoQ10 really does slow decline in total functional capacity for a person in the early stages of HD.

Are there other drugs being tested by the Huntington’s Study Group?

The pace of clinical exploration continues to accelerate, with a growing number of drugs and compounds being tested through clinical trials:

Riluzole is currently used in the treatment of ALS. The results of RIDHD (a small multi-centre trial to test the effect of riluzole on persons with HD) are expected shortly.

Creatine was shown to extend survival by 20% in a mouse model. CRESTHD is a clinical trial to determine creatine’s ability to slow the progression of HD in humans. Results are expected shortly.

Minocycline was shown to extend survival by 14% in a mouse model. MINO is an 8-week safety and tolerability study for the use of minocycline in humans which should be launched shortly.

Separate from the work of the Huntington’s Study Group, Laxdale Pharmaceuticals is conducting a human drug trial of a new compound called LAX-101. This drug may help to protect the membrane of brain cells from damage caused by oxidation, and may help to alter the course of HD. The results of the test are expected by the end of 2002 or earlier.

Conclusion

While it is disappointing that CARE-HD did not yield more positive results, the trial is nevertheless a source of encouragement for the HD community.

First, the trial demonstrates that the Huntington’s Study Group is an effective organization with respect to identifying potential therapeutic options, and testing them through large-scale, multi-centre drug trials.

Second, the research community is now in a position to focus additional resources on other options. Other drug trials, such as those examining riluzole, creatine, and minocycline may yet yield positive results, and will require significant resources if successful.