Projects & Affiliations

TRIAL OF VITAMIN E IN PEOPLE WITH DOWN SYNDROME

An international research study

Participants must be:

50 years of age or older
Medically stable
Have a caregiver that also can take part

We offer:

Thorough health examinations

Free vitamins

Payment for taking part

Contact Ann

Phone: (416) 925-5141 ext. 360
E-mail: vitE@SurreyPlace.on.ca

RECRUITMENT INFORMATION

The Multicentre Vitamin E Trial in People with Down Syndrome is a multi-site collaborative project. The project will recruit 400 adults with Down syndrome age 50 years of age and over through approximately 20 sites across the USA and international countries such as England, Ireland, Wales, and Canada. Surrey Place Centre is one of the participating sites. The project is a part of a research program funded by the National Institutes of Health (USA).

Purpose of the Research Project

The aim of the program is to find out whether high dose vitamin E pills (1000 international units twice daily), taken every day for 3 year, will stop or slow down some of the memory and changes in daily living skills that occur in persons with Down syndrome as they get older. These changes are referred to as dementia of the Alzheimer type (DAT). This will be the first large-scale treatment study of DAT in Down syndrome. It will serve as a model for future efforts at applying treatments developed for sporadic Alzheimer disease to older persons with Down syndrome. The dose of vitamin E in this study is 40 times the amount that is in a typical multivitamin pill.

Design of the Project

Individuals with Down syndrome 50 years of age or older at all levels of intellectual functioning who meet the study inclusion and exclusion criteria will be eligible for enrollment. Participation of an individual who will come to the study visits, supervise the taking of the medication, and be available for telephone interview between study visits, also is required. This individual may be the primary caregiver or a designate. In some cases, it may be convenient for more than one person to assist the participant. The proposed project involves less than minimal risk and it does not involve testing of a new drug. Consent (assent) from the participant and from their primary caregiver both are required for participation. There are two sets of consent/assent forms. The first set will be needed to give the service provider(s) permission to review personal files to complete a health status check list to determine if a possible participant might be eligible for the study and to give such information to the research team, and/or to give the research team permission to review personal files prior to the screening visit if the service provider does not have the time to do this. The second set of consent forms is needed to give the research team permission to carry out the screening procedure and the clinical trial.

Inclusion Criteria

Presence of clinically confirmed Down syndrome
Appropriately signed and witnessed assent forms from prospective participants and consent forms from caregiver
Age 50 years or older at the start of the protocol
Medically stable
Medications stable for at least one month prior to entry into the project
Involvement/cooperation of informant/caregiver

Exclusion Criteria

Medical/neurological condition associated with dementia (other than dementia of the Alzheimer type)
Modified Hachinski score>4
Deficits (e.g., hearing, visual) which interfere with testing
Major depression within 3 months
Blood clotting disorder
Current use of anticoagulants (these prevent the blood from clotting)
Regular use (more than two doses per week) of non-steroidal anti-inflammatory drugs within 3 months (use of aspirin 325 mg daily or less is permitted)
Use of experimental medications within 3 months except for Aricept
Regular use of vitamin E greater than 50 units per day during the previous 6 months
Stable use of cholinesterase inhibitors and/or estrogen is permitted (if regimen has not changed in past 3 months)
History of allergy to vitamin E

Screening Evaluation

Interview with informant/caregiver
Review of medical history and current medications
Blood work including hematology, chemistry, and thyroid function (see below). For these tests, 30 ml (about two tablespoons) will be taken by an experienced phlebotomist from an arm vein. If for example, blood tests indicate hypothyroidism, replacement therapy would be required with normalization of values, and stable hormone dose for at least1 month. At the time the blood is drawn for laboratory tests, one small tube will be taken for research (see below).
Physical examination
Tests of memory, skills, and every day behaviour
Assessment of DSM-IV criteria for probable Alzheimer disease
Modified Hachinski

Visit 1 will usually occur at 2-3 weeks after screening evaluation. After screening evaluation, if the participant is approved, he/she will be assigned randomly into either the treatment or placebo group. This means that each participant will have approximately an equal chance of being assigned to receive either the high dose vitamin E pills (1000 IU, twice a day) or placebo (inactive pills). Neither the study participants nor the local research team will know who is receiving active medication or placebo. All participants will receive multivitamins to take. The same tests of memory, skills, and every day behaviour, as in the screening visit, will be administered. A brief physical examination will be performed and vital signs will be measured.

Visits 2-5 will occur every six months for a period of 30 months. These visits are to ensure that the participant's study vitamin supplement is being adequately tolerated. The same procedures will be followed as were done during visit 1. Cognitive and behavioural tests will be given. Vital signs will be measured and a brief physical examination will be performed. During these visits, blood will not be collected as in the screening visit. At each visit, a six-month supply of study medication will be dispensed. A phone contact will be made after 3 months of each visit. If for some reasons, the participants can't make these visits, our nurse and research staff might make site visits.

Visit 6 will occur six months after visit 5. The participant will have a final physical examination and take memory and behaviour tests similar to those taken during previous visits. Two blood samples (a total of about 3 tablespoons) will again be collected for medical and biochemical tests.

Compensation

The participant and the caregiver who assists the participant to take part in the study and to supervise taking of the study medication will each receive $30 for each visit (including the screening visit, the baseline visit and every 6 month visit). If the full study is completed, the participant and their caregiver will each receive an additional $50.

Schedule of Procedures

Table 1 provides a summary of the proposed schedule for each potential participant from the time of the Screen, one month before collection of research data at Baseline and at subsequent semi-annual visits for three years. Each procedure is identified in the first column and "X" identifies which procedures are administered for each visit numbered from 1 to 8 in the second row.

Additional Information

Each study visit will take about 1 hour. The research team will try not to let participants become tired. Participants will be offered a snack.

This clinical trial is not a service program. In particular, it is not intended to diagnose dementia. There will be no formal, direct, feedback from the site tests. If problems are discovered in any health domains, appropriate action will be taken and the participant's doctor will be contacted. All questions about the study will be answered.

All members of the research team are qualified to do the tests of memory, skills and every day behaviour. This will be done at Surrey Place Centre, usually by Ann Lovering, R.N. Other members of the team may assist with interpretation.

Videos may be made of the memory and skills testing to aid with interpretation, but only if consent is provided by the participant and the caregiver. These will be housed under lock and key in the vitamin E cabinet at Surrey Place Centre. Video files made for this research project will be subject to the same regulations as those made for clinical evaluation. If permission is granted, videos may be kept after the study for additional teaching and research purposes.

The research dose of vitamin E is 40 times that in a standard one-a-day multivitamin pill. Serious side effects are very rare. Sometimes people complain about slight stomach or intestinal cramps, mild diarrhea, or queasiness when taking the research dose of vitamin E. These effects do not last and no treatment is given. The pills can be swallowed easily, particularly if given in applesauce. If people cannot tolerate the medication that is to be taken, then they will have to drop out of the study. Any symptoms that even possibly might be side effects from the medication will be reported as an Adverse Event.

The Surrey Place Centre Research and Ethics Review Board Contact is Brad Littleproud (416 925-5141) or designate in his absence.

The clinical laboratory tests that will be conducted on the blood samples include complete blood cell count, BUN, creatinine, total protein, albumin, calcium, liver chemistries, TSH (or free thyroxine index), B12, folate, RPR, and prothrombin time. The blood sample for research will be used to determine the apolipoprotein E (ApoE) phenotype and antioxidant levels. This information is of no personal benefit. ApoE tends to prevent inflammation in the body. Some variants of it actually have antioxidant properties. Thus research information obtained from analysis of the research blood sample will help with interpretation of the results of the study. Donating the blood sample for research is optional. This will not be used for any other purpose than described above. It will be destroyed after the tests have been completed.

An information booklet intended for possible participants and their caregivers, as well as flash cards and videotapes demonstrating the research psychometric tests that will be done, are available. The booklet will be provided in the standard information package to interested participants. Other material is available upon request. Flash cards will be shown at the first interview. All information may be used at interviews or presentations.

The Surrey Place Centre Research and Ethics Review Board Contact is Brad Littleproud.

Members of the research team will answer all questions about the study and will be delighted to interview organizations and prospective participants prior to the screening visit and/or to give live presentations to groups.

Contact

Service providers and/or careproviders should respond to the Study Coordinator

Ann Lovering

Phone (416) 925-5141, ext. 360 or (416) 925-2169, ext. 360

E-Mail vitE@SurreyPlace.on.ca