Multiple Sclerosis
Conditions
Keywords
fasting, Mediterranean diet, body composition, quality of life
Brief summary
In the proposed study, investigators will assess the safety and feasibility of cycles of a fasting mimicking diet (FMD) and its effect on Multiple Sclerosis Quality of Life (MSQOL) in relapsing MS (RMS) patients treated with standard disease modifying therapies (FMDMS). To test the primary hypothesis, investigators will compare the composite quality of life score in terms of improvement in disability, fatigue, and cognitive function with the fasting protocol, as compared to a Mediterranean diet (control) group alone. Further, investigators hypothesize that the effects will remain for at least 6-months after the last FMD cycle. The Mediterranean diet (MD) has been chosen as the control diet to minimize baseline dietary differences among patients. It has been trialed for feasibility in Multiple Sclerosis patients and used in a previous human FMD trial for MS patients where a FMD followed by MD was shown to have positive effects on people with MS.
Detailed description
The study design is a cross-over randomized, controlled trial that includes two arms in which all patients will be on a MD for twelve months. One group will be on MD alone for 6 months and then do 3 rounds of a standardized 7-day FMD dietary regimen every 2 months. The other group will do the 3 cycles of FMD during the first 6 months, and the subsequent 6 months on the MD alone. This will allow investigators to test FMD effects on a defined background diet as well as tease out the effects of that diet alone. In addition, investigators will be able to assess long term effects of a FMD on an autoimmune disease. Preliminary data from a phase I clinical study in MS suggest that a FMD is safe, feasible, and potentially effective in relapsing-remitting multiple sclerosis (RRMS) patients (registered in Clinical Trials ID: NCT01538355). This study demonstrated a positive effect on health-related quality of life (HRQOL) components and a small effect on disability after one round FMD followed by a Mediterranean diet for 5 months. A successful trial will provide relevant information about the efficacy and safety of these dietary interventions in MS patients and help confirm the positive effects seen in previous studies. In addition it is designed to elucidate the physiologic and immunologic effects of dietary changes and could help clarify the complex interactions between nutrition and autoimmune disease.
Interventions
OTHERMed Diet. Investigators would like to see what differences a Mediterranean Diet makes to the status of patients with Multiple Sclerosis.
In one group investigators will look at the Med diet alone for 6 months. Then investigators will have the patients add on 3 rounds of FMD. In the other group, patients will do Med diet and FMD for 6 months followed by Med diet alone for 6 months. This will allow investigators to look for a diminution in effect of the Med diet 6 months after the last FMD.
Sponsors
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of MS (AJ Thompson et al 2018) * Able to give informed consent * Able to tolerate MRI * Age 18 to 55 years * Disease duration 6 months to 20 years (included) * EDSS 0 to 6 * No change in immunomodulatory therapy in the 6 months prior to enrollment (not on immunomodulatory therapy is acceptable) * No glucocorticoid use within 30 days prior to screening * No serologic evidence of vitamin B12 deficiency or hypothyroidism * No Vitamin D deficiency (\< 30 ng/ml)
Exclusion criteria
* Relapse \< 60 days. * Any active or chronic infection (e.g. HIV, Syphilis, untreated TB) * Previous history of a malignancy other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year * Severely limited life expectancy by another co-morbid illness * History of previous diagnosis of myelodysplasia or previous hematologic disease or current clinically relevant abnormalities of white blood cell counts * Pregnancy or risk of pregnancy (this includes patients who are unwilling to practice active contraception during the duration of the study) * eGFR \< 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination * Inability to give written informed consent in accordance with research ethics board guidelines * Known alimentary allergy or intolerance to any of the ingredients of the FMD regimen or the presence of diabetes * Underweight
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Health-related Quality of Life (HRQOL) | 12 months | Improvement in disability, fatigue and cognitive function. Scale and composite scores range from 0 to 100, where a higher score indicates a better QOL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the effect on clinical measures of neurological status: Annualized relapse rate | 12 months | Relapses will be verified by clinical visit, history, and possible imaging. Rates will be analyzed per year |
| To evaluate the effect on clinical measures of neurological status: EDSS | 12 months | Expanded disability status score (EDSS): A verified instrument to verify the disability of the patient. The score range from 0-10 with larger numbers indicating worse disability. |
| To evaluate the effect on clinical measures of neurological status: depression, anxiety | 12 months | We will assess anxiety and depression using Hospital Anxiety and Depression Scale (HADS). The score range from 0-21 with smaller numbers being better |
| To evaluate body composition | 12 months | Changes in body composition: BMI (Weight and height will be combined to report BMI: kg/m\^2) |
| Assessing Safety and Tolerability of a FMD in MS: Compliance and Serious Adverse Events | 12 months | To evaluate the safety and tolerability of a FMD will be assessed using assessed using a standardized safety questionnaire. Adverse events will be scored utilizing Common Terminology Criteria for Adverse Events (CTCAE) |
| To estimate changes in measures of disease activity in the central nervous system (CNS) | 12 months | Number and volume of new and enlarging lesions detected by MRI. Units Cm\^2 |
| To evaluate alterations in immune function by assessing changes in cell counts, serum cytokines and secretion patterns, with a focus on pro-inflammatory cytokines IL-2, interferon-gamma (IFNγ), and IL-17A, and the regulatory cytokine, IL-10. Units: pg/mL | 12 months | It is known that lymphocyte counts decrease during fasting. |
| To evaluate changes following the FMD in the composition and function of the gut microbiota which influences immune function in the T and B cells compartment in the blood. | 12 months | It has been shown that patients with MS have moderate alterations of gut microbial communities. Units: μm |
| To evaluate IGF-1 changes | 12 months | Changes in Insulin like growth factor 1 (IGF-1) (ng/mL) which measure FMD effectiveness and a lower animal protein intake. |
Countries
United States
Contacts
Primary ContactFrida Hovik, MS RDN
Outcome results
None listed