Multiple Sclerosis and the Effects of Ketogenic Diet Therapy

NCT06715436 | Recruiting

• 1 other identifier: KETOMED-MS-2024
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple sclerosis (MS) is an inflammatory and immune-mediated neurological disease with multifactorial etiology. The specific etiopathogenetic mechanisms of MS are still unknown but it is clear that it results from a combination of genetic and environmental factors. Several studies have reported the possible role of diet as a risk factor for MS and its progression. To date, many dietary patterns and their association with MS have been studied, but data is still limited and inconclusive. Mediterranean Diet (MedDiet) has been associated with a lower risk of developing MS, compared to a Western-style diet. In one of investigators' studies, higher MedDiet adherence was associated with a 6-fold greater likelihood of having lower disease severity than those with low adherence. A significant restriction of carbohydrates (up to ketogenesis) can have beneficial effects on various parameters (inflammatory markers, oxidative stress, altered glucose metabolism) which are altered in subjects with MS. Ketogenic diet therapies (KDTs) have been recommended mainly for children with drug-resistant epilepsy, but in recent years they have been applied to Multiple Sclerosis. Preclinical studies in animal models evaluating the efficacy of KDTs in experimental autoimmune encephalomyelitis (EAE) found a beneficial effect of diet in slowing of disease progression, improvement of motor disability, reduction of inflammatory cytokines and reactive oxygen species. In a randomized study, improvements in health-related quality of life (HRQL) scores and a slight decrease in EDSS scores were found. An open-label, single-arm study of 20 patients with RRMS also reported that, after 6 months of MAD, no subjects had new or enlarging FLAIR/T2 lesions, with a significant improvement in the EDSS score, the Modified Fatigue Impact Scale subscales and arm. A 3-arm parallel-arm randomized controlled pilot study was planned to determine the effectiveness of a modified Atkins diet (MAD) compared to a Mediterranean diet (MedDiet) on quality of life in a population with MS.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

Multiple Sclerosis; Ketogenic Dietary Therapy; Mediterranean diet

Outcome Measures

Primary Outcomes (1)

• The CPH subscale of the Multiple Sclerosis Quality of Life-54 (MSQoL -54)

  Quality of life will be assessed in terms of physical health referring to the CPH subscale of the MSQoL -54 after 6 months of treatment. ITS consists of 52 items grouped in 12 subscales plus two single items. All scores are transformed to scale from 0-100 and then added within each subscale to obtain the subtotal. By dividing the subtotal by the number of responses, the final score of the subscale is obtained. The scores final are in turn multiplied by a specific number at each subscale; adding the scores transformed in this way there is a value for "physical health" and one for "mental health". These two values, added, give the final score of the MSQoL-54. The higher scores demonstrate better HRQoL in patients.

  Evaluation at baseline and after 6 months

Secondary Outcomes (5)

• Expanded Disability Status Scale (EDSS)

  Evaluation at baseline and after 6 months

• Multiple Sclerosis Functional Composite (MSFC)

  Evaluation at baseline and after 6 months

• Modified Fatigue Impact Scale (MFIS)

  Evaluation at baseline and after 6 months

• The Pittsburgh Sleep Quality Index

  Evaluation at baseline and after 6 months

• The Beck Depression Inventory

  Evaluation at baseline and after 6 months

Study Arms (3)

Mediterranean Diet

OTHER

The MedDiet will be planned according to the Mediterranean diet pyramid. Energy prescriptions will be tailored to each patient's specific needs. The initial calorie prescription will be calculated taking into account usual dietary intake REE and physical activity level (PAL). Changes to calorie prescriptions will be made as needed during the course of follow-up. A minimum of 0.8-1 g of animal protein (e.g. eggs, milk, meat, poultry and fish) per kilogram of body weight per day will be given.

Dietary Supplement: Mediterranean Diet

Ketogenic Diet

EXPERIMENTAL

Modified Atkins diet with a maximum of 20 g of carbohydrates per day. Fat-rich foods of plant origin will be encouraged in order to reach the prescribed daily caloric intake. Energy prescriptions will be tailored on each patient's specific requirements. The initial calorie prescription will be based on an average between the pre-diet intake, REE and physical activity levels. A minimum of 0.8-1 g of protein from animal sources (e.g. eggs, milk, meat, poultry and fish) per kilogram of body weight per day will be given.

Dietary Supplement: Ketogenic Diet

Control group

OTHER

The control group will be asked to continue their dietary and lifestyle habits.

Dietary Supplement: Control group

Interventions

Mediterranean Diet DIETARY_SUPPLEMENT

The MedDiet will be planned according to the Mediterranean diet pyramid

Mediterranean Diet

Ketogenic Diet DIETARY_SUPPLEMENT

Modified Atkins diet with a maximum of 20 g of carbohydrates per day.

Ketogenic Diet

Control group DIETARY_SUPPLEMENT

The control group will be asked to continue their dietary and lifestyle habits

Control group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of relapsing-remitting MS (RRMS) or progressive MS (PMS)
• Age between 18 and 60 years
• BMI between 18.5 kg/m2 and 39.9 kg/m2
• If on disease-modifying drugs, stable for 6 months, or no use of drugs in the previous 6 months
• Ability to give verbal and written consent

You may not qualify if:

• Patients actively engaged in a weight loss program or other specific diet (e.g. vegetarian, vegan); patients not willing to follow the assigned dietary pattern or patients with high adherence to MedDiet (MediLite score \> 14)
• Pregnancy or breastfeeding
• Relapse or cortisone treatment within 30 days before study entry
• Clinically relevant metabolic, progressive or malignant diseases
• Intake of \> 1 g/day of omega-3 fatty acid supplements
• Underweight (BMI\<18.5 kg/m2) or severe obesity
• Significant cognitive-cooperative impairment
• Insulin-dependent diabetes mellitus (type I)
• Weight loss greater than 5 kg within 2 months prior to study entry
• Diagnosis or suspicion of an eating disorder
• Kidney stones
• Oral anticoagulant therapy
• Known alcohol and drug abuse
• Telephonic interviews will be performed monthly to evaluate adherence to the dietary treatment and/or whether any changes in supplements use, physical activity, nutrition habits.

Sponsors & Collaborators

• IRCCS National Neurological Institute "C. Mondino" Foundation: lead
• University of Pavia: collaborator

Study Sites (1)

U.O.Sclerosi Multipla

Pavia, 27100, Italy

RECRUITING

Related Publications (23)

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  PMID: 37764792 RESULT

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Diet, Mediterranean; Diet, Ketogenic; Control Groups

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Diet, Carbohydrate-Restricted; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Eleonora Tavazzi, MD

  U.O. Sclerosi Multipla

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eleonora Tavazzi, MD

CONTACT

0382380385; eleonora.tavazzi@mondino.it

Cinzia Fattore, MD

CONTACT

0382380385; cinzia.fattore@mondino.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2024
• First Posted: December 4, 2024
• Study Start: March 15, 2024
• Primary Completion: March 15, 2025
• Study Completion: September 15, 2025
• Last Updated: December 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)