Huntington Society of Canada

CARE-HD Study Results - Frequently Asked Questions and Answers

Background

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

(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).

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

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.

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 disease.

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

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 an 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).

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 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 disease, the drug is no longer available for individuals with HD.

The results of the CARE-HD study cannot be applied to persons at risk for HD or who are pre-symptomatic.

In addition, 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 disease, the drug will not be prescribed to persons with HD, or who are risk or presymptomatic.

Remacemide was shown to have no benefit for persons in the early stages of Huntington disease.

In addition, 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 disease, the drug will not be prescribed for persons with HD, or who are at risk or presymptomatic.

The results of the CARE-HD study cannot be applied to persons who are in the intermediate stages of HD.

In addition, 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 disease, the drug will not be prescribed for persons with HD, or who are at risk or presymptomatic.

The results of the CARE-HD study cannot be applied to persons who are in the advanced stages of HD.

In addition, 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 disease, the drug will not be prescribed for persons with HD, or who are at risk or presymptomatic.

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 Disease Society of America (HDSA), the Huntington 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.

The results of the CARE-HD study cannot be applied to persons at risk for HD or who are pre-symptomatic.

In addition, 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.

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.

The results of the CARE-HD study cannot be applied to persons who are in the intermediate stages of HD.

In addition, 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.

The results of the CARE-HD study cannot be applied to persons who are in the advanced stages of HD.

In addition, 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.

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 disease.

For more information about issues associated with CoQ10, contact the Huntington Society of Canada at 1-800-998-7398 or at [email protected]

After August 14, 2001, the statistical detail concerning the study results will be published and made available to the public.

The Huntington Study Group is hoping to conduct follow-up studies to better establish whether or not CoQ10 really does slow decline in the for a person in the early stages of HD.

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 RID-HD (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. CREST-HD 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. MIDAS-HD 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 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.

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 Study Group is an effective organization with respect to identifying potential therapeutic options, and testing them through large-scale, multi-centre drug trials. Since part of the Huntington Society of Canada's research funding goes to the Huntington Study Group, we should be pleased that the Society is supporting an organization that is so effective.

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.