Research

Introduction

Direct-MS has two main goals:

The compilation and distribution of reliable, science-based information on the linkages between nutritional factors and multiple sclerosis.
The promotion and support of scientific research which advances knowledge of linkages between nutritional factors and multiple sclerosis and the value of nutrition-based treatments for MS.

On the basis of diverse data such as immunological studies, animal experiments and epidemiology as well as theoretical deductions from the established immunological pathogenesis of the MS disease process and the principles of evolutionary biology, Direct-MS has proposed that various nutritional strategies may well be very beneficial for persons with MS. However, due to various financial and sociological factors, no proper clinical research has ever been done to test the effectiveness of such science-based, nutritional strategies. Thus there is considerable uncertainty as to the value of nutrition-based treatments.

The second goal of Direct-MS is most important because clinical research will lead to the acceptance or rejection of proposed nutrition-based therapies for treating multiple sclerosis and preventing it in the first place. Such scientific knowledge is urgently needed to eliminate the current uncertainty regarding the value of nutritional strategies and to provide persons with MS with sufficient information to make a proper decision in regards to the use of such strategies.

Research Proposals

Direct-MS is open to receiving research proposals related to nutrition and MS at any time. Both MS researchers and a panel of persons with MS will evaluate all proposals to ensure such research is scientifically valid and is of potential value for persons with MS. Acceptance or rejection of a proposal will be decided within a month of receipt. Proposals can be either emailed to aembry@direct-ms.org or mailed to Direct-MS, 5119 Brockington Rd NW, Calgary, AB, Canada, T2L 1R7.

Current Research

Direct-MS is currently funding two nutrition-related clinical trials. Both are being undertaken by established MS researchers and are being done with the same scientific rigour as a drug trial. One is a small, controlled and randomized trial that will test the effectiveness of the recommended nutritional strategies for decreasing MS disease activity. The other is a dose/safety study of vitamin D for multiple sclerosis. Both these studies will yield important information on the relationship between MS and nutritional factors and will potentially lead to larger clinical trials involving the use of one or more nutritional strategies as a treatment for MS.

Summaries of each of these on going clinical trials are below. Please feel free to contact us at info@diect-ms.org if you have any questions or comments regarding these Direct-MS sponsored clinical trials.

A Dose/Safety Study of Vitamin D for Persons with Multiple Sclerosis

Introduction – Beginning in 2000, Direct-MS has strongly advocated the use of adequate vitamin D supplementation for the prevention and treatment of multiple sclerosis. Since that time we have also actively promoted the need for clinical research to test the effectiveness of vitamin D for preventing and treating MS. Before clinical trials to test the efficacy of vitamin D for MS can be done, it is necessary to determine the optimal dosage of vitamin D to use in such a trial. Direct-MS chose to fund this preliminary “Dose/Safety” study for vitamin D to ensure that the necessary clinical research on the efficacy of vitamin D for MS happens as soon as possible.

Leaders – The chief investigator of the clinical research is Dr Paul O’Connor, Clinical and Research Neurologist, Chief, Division of Neurology and Director of the MS Centre at St Michael’s Hospital in Toronto. Dr O’Connor has assembled a large and impressive team of researchers for this trial. They include Dr Jodie Burton, Co-investigator, MS Clinical Fellow, St. Michael’s Hospital, University of Toronto; Dr Melanie Ursell, Co-investigator, Staff, Division of Neurology, St. Michael’s Hospital; Dr Reinhold Vieth, Co-investigator. Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto; Samantha Kimball, Co-investigator. Master of Science Student, Department of Nutritional Sciences, University of Toronto; Dr. Louise Thibault Professor, School of Dietetics and Human Nutrition, McGill University, Montreal; Sally Kilborn, Master of Science Student, School of Dietetics and Human Nutrition, McGill University; Dr. H. Michael Dosch, Co-investigator. Professor of Immunology, University of Toronto and the Hospital for Sick Children, Toronto; Dr Amit Bar-Or, Co-investigator. Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal; Dr Cheryl D’Souza, Centre for Research in Neurodegenerative Diseases, University of Toronto.

Ethics – The study has been approved by the Ethics Boards of St Michael’s Hospital and McGill University.

Goals – The main goal of the study is to determine the optimal dose of vitamin D to use in a subsequent clinical trial which will test the efficacy of vitamin D for affecting disease activity in MS. Such an optimal dose will be the maximum dose which is well tolerated without any adverse side effects and which also has a significant effect on immune activity. A second objective is to determine if there are any positive effects of higher doses of vitamin D3 on bone health in people with MS. A third objective is to examine the relationship between diet and MS especially vitamin D intake from food sources. A fourth objective is to examine the effect of vitamin D on mood and feelings of well-being of the participants.

Methods – The study will involve 30 participants, all of whom have MS (RRMS, SPMS or PPMS) and will last one year. Each participant will be given an increasing dose of vitamin D3 starting at 28,000 IU per week (4000 IU/d). The dose of vitamin D3 will be gradually increased every 2 to 6 weeks to the highest dose of 280,000 IU per week (40,000 IU per day). After the highest dose is taken for 6 weeks, the dose of vitamin D3 will be lowered to a maintenance dose of 70,000 IU per week (10,000 IU per day) that will be taken for 12 weeks. The dose of vitamin D3 will then be lowered again to 28,000 IU per week (4000 IU per day) taken for another 8 weeks. 1200 mg of calcium will be taken daily during the entire study. Blood and urine samples will be obtained every month and analyzed to determine if any anomalous calcium or creatinine/calcium ratios are present in any of the participants. The blood samples will also be analyzed for immunological markers of inflammation and blood brain barrier integrity (cytokine profiles, lymphocyte response measures and matrix metalloproteinases) and the proportion of change in bone turnover markers. Measures of well being will be assessed using the Hospital Anxiety and Depression Scale questionnaire. To examine dietary habits and amounts of nutrients participants get in the diet, particularly vitamin D, they will be asked to complete a “Food Frequency Questionnaire”. In addition, a “24-hour recall” food questionnaire will be given.

Results – The blood tests will determine if high doses of vitamin D3 have any adverse effects on calcium levels in the body. Such adverse effects include the elevation of serum calcium levels above normalized ranges (range 2.1-2.6 millimoles per liter) or urinary calcium:creatinine ratios above 1.0. The measurement of immunological markers will allow the determination of the effects of the various doses of vitamin D3 on immune activity. These two data sets will allow an optimal dose of vitamin D to be determined. Such a dose will be used in subsequent clinical trials for MS and possibly other diseases related to vitamin D deficiency (e.g. prostate cancer). The other studies mentioned above will provide insight into the value of higher doses of vitamin D for preventing and treating osteoporosis and for treating depression.

Discussion – This clinical trial is basically a “Phase I” trial meaning it is designed to determine the metabolism and pharmacologic action of vitamin D3 in humans, the side effects associated with increasing doses, and evidence of effectiveness for treating immune reactions related to MS disease activity. Such a trial must be done before any proper clinical trial on the effectiveness of optimal doses of vitamin D for treating MS can be initiated.

Testing the Effectiveness of the Best Bet Diet for Decreasing Disease Activity in Multiple Sclerosis

Introduction – Direct-MS is very pleased to be funding a rigorous clinical trial which will test the effectiveness of the Direct-MS recommended nutritional strategies, often referred to as the Best Bet Diet for MS (BBD), for affecting MS disease activity. Such research is of critical importance for determining if the recommended nutritional strategies are of value for MS and thus worth serious consideration as a therapeutic option. Recruitment for the trial began in July, 2006 and it is hoped that results will be available early in 2008.

Leaders – The chief investigator of the clinical research is Dr Jonathan O’Riordan, Consultant Neurologist and Director of Tayside MS Regional Service and Research Unit, Ninewells Hospital, Dundee, Scotland. The principle investigator and study doctor is Dr. Pushkar S. Shah, Registrar and Research Fellow, MS Research Unit, Dept. of Neurology, Ninewells Hospital, Dundee. The MS Research Coordinator is Mrs. Sally Wilson also of Ninewells Hospital.

Ethics – The study has been approved by the Ethics Board of Ninewells Hospital. It will be conducted in accordance the European Clinical Trials Directive and associated guidelines, the International Conference on Harmonization Guidelines on Good Clinical Practice and the Principles of the Declaration of Helsinki, as well as all other national and local laws and regulations.

Goal – The main goal of the study is to compare the effectiveness of the Best Bet Diet for MS (BBD) with that of the dietary advice provided by the MS Society of Britain for decreasing MS disease activity over one year of use.

Methods – The study will involve 30 participants, all of whom have relapsing-remitting MS and EDSS disability between 0 and 3.5. Fifteen participants will be randomly assigned to the BBD and the other 15 to the dietary advice of the MS Society. The study will last one year and each participant will have an MRI scan at baseline, 2 months, 4 months, 6 months and at 1 year. The MRI scans will measure T1 and T2 lesions as well as brain volume. The participants will also have a complete physical and neurological examination at baseline, 6 months and 1 year. At these times disability will be measured using the EDSS (Expanded Disability Status Scale) and MSFC (MS Functional Composite) scales. At baseline and every 4 weeks the participants will complete questionnaires including a Fatigue Severity Scale (FSS), MS Quality of Life Inventory (MSQLI) and Patient Global Assessment (PGA).

Best Bet Diet Nutritional Protocol

Eat fruits and vegetables for carbohydrates and micro-nutrients
Eat fish and skinless breast of chicken and turkey, for protein
Eat extra virgin olive oil for fats
Avoid all dairy, grains (except rice), legumes
Avoid all allergenic foods, which are identified by skin and ELISA tests
Avoid all red meat and margarine

Supplements:

Grape seed extract 2 capsules/day
VitaminD3 2000 IU/day in summer and 4000 IU/day in winter
Calcium 1200 mg/day
Vitamin A 5000 IU/day
10 grams salmon oil
Vitamin B-complex 50 mg/day
500 mcg of B-12
1 g of vitamin C
400 IU of vitamin E
up to 750 mg of magnesium (a good Ca/Mg ratio is 2:1)
25 mg of zinc
1 mg of copper
200 mcg of selenium
Manganese 20 mg/day
up to 5 g of evening primrose oil or borage oil
4 capsules of acidophilus
4 capsules of enzymes
500 - 1000 mg of Lecithin
Ginkgo biloba 120 mg/day
Co-enzyme Q10 60 mg/day

MS Society of Britain Dietary Advice

Five portions of fruit or vegetables every day including one portion of dark green, leafy vegetables
Use polyunsaturated margarine and oils such as sunflower oil or corn oil, instead of saturated fat such as lard and butter
Grill, Bake, steam or poach food instead of frying
Choose lean cuts of meat. Avoid sausages, pates and beefburgers, as they are often high in saturated fat
Avoid too much saturated fat and hydrogenated vegetable oil in foods like pastry, cakes and chocolate
Eat at least two portions of fish a week, one of which should be oily fish like mackerel, pilchards, salmon or sardines
Use low fat dairy products such as skimmed milk, low-fat yoghurt or low fat cheeses
Eat whole meal bread and whole grain cereals
Drink six to eight cups of fluid daily (about 1.5 litres). Don’t rely on high-caffeine drinks, such as coffee, tea and cola.

Monitoring Dietary Compliance – The participants will complete food diaries every 3 months and, in-between the visits to the clinic, subjects will be given reminders via phone and letters. They will also have daily access to the research unit for dietary advice.

Results – The effects on MS disease activity after one year will be assessed through the measured changes in disability scores, brain volume and lesion load. An assessment of symptom control and quality of life will be obtained from the completed questionnaires. The various results from those participants on the BBD will be statistically compared with the results from those following the dietary advice of the MS Society to determine if the BBD has a measurable positive effect on MS disease activity.

Discussion – This clinical trial is basically a “Phase I/II” trial and will determine if the BBD has a measurable effect on MS disease activity and if such dietary research can be accomplished in a scientifically acceptable manner. If positive results are obtained, a larger trial, involving up to 100 participants in each arm, will be necessary to confirm the positive effect of the BBD and to allow a better assessment of the strength of that effect.