Effect of Low Histamine-Based Modified Mediterranean Diet in Multiple Sclerosis

NCT07501520 | Completed

• 2 other identifiers: 2023/03-26223S505
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized controlled trial will evaluate the effects of a low histamine-based modified Mediterranean diet in adults with relapsing-remitting multiple sclerosis (RRMS). The study will compare three groups: a low-histamine modified Mediterranean diet, a traditional Mediterranean diet, and a control group without dietary intervention. The main outcomes include clinical measures such as disability status, fatigue, migraine, gastrointestinal symptoms, and quality of life, as well as blood markers including plasma histamine, diamine oxidase activity, total antioxidant capacity, and oxidative stress indicators. The goal is to determine whether reducing dietary histamine within a Mediterranean diet pattern provides additional benefits beyond a traditional Mediterranean diet in improving symptoms and biological markers related to inflammation and oxidative stress in RRMS.

Conditions

Multiple Sclerosis (MS) - Relapsing-remitting; Mediterranean Diet

Keywords

Relapsing-Remitting Multiple Sclerosis; Mediterranean Diet; Low Histamine Diet; Fatigue; Oxidative Stress; Diamine Oxidase; Quality of Life

Outcome Measures

Primary Outcomes (1)

• Change in fatigue severity (Fatigue Severity Scale [FSS]; scale range: 9-63; higher scores indicate greater fatigue)

  Fatigue will be assessed using the Fatigue Severity Scale (FSS). Higher scores indicate greater fatigue. The primary outcome is the change in FSS score from baseline to the end of the intervention across the three study groups.

  From baseline to 12 weeks

Secondary Outcomes (6)

• Change in disability status (Expanded Disability Status Scale [EDSS]; scale range: 0-10; higher scores indicate greater disability)

  From baseline to 12 weeks

• Change in health-related quality of life (36-Item Short Form Survey [SF-36]; scale range: 0-100 per domain; higher scores indicate better health-related quality of life)

  From baseline to 12 weeks

• Change in serum total antioxidant capacity

  From baseline to 12 weeks

• Change in oxidative stress markers (e.g., malondialdehyde)

  From baseline to 12 weeks

• Change in plasma histamine levels

  From baseline to 12 weeks

Study Arms (3)

Low Histamine-Based Modified Mediterranean Diet

EXPERIMENTAL

Participants receive a low histamine-based modified Mediterranean diet with restriction of high-histamine and histamine-releasing foods while preserving core Mediterranean diet principles.

Behavioral: Low Histamine-Based Modified Mediterranean Diet

Traditional Mediterranean Diet" Arm Description

ACTIVE COMPARATOR

Participants receive a traditional Mediterranean diet without specific histamine-related restrictions.

Behavioral: Traditional Mediterranean Diet

Control (Usual Diet)

NO INTERVENTION

Participants continue their usual diet and do not receive a structured dietary intervention.

Interventions

Low Histamine-Based Modified Mediterranean Diet BEHAVIORAL

Structured dietary program based on the Mediterranean diet with restriction of high-histamine and histamine-releasing foods (e.g., aged cheeses, processed meats, certain fish, fermented products, vinegar, some fruits and vegetables.

Low Histamine-Based Modified Mediterranean Diet

Traditional Mediterranean Diet BEHAVIORAL

Structured dietary program following a traditional Mediterranean diet rich in vegetables, fruits, whole grains, legumes, olive oil, and fish, without specific histamine-related restrictions.

Traditional Mediterranean Diet" Arm Description

Eligibility Criteria

• Age: 19 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 19 to 64 years.
• Diagnosis of relapsing-remitting multiple sclerosis (RRMS) according to 2017 McDonald criteria.
• EDSS score \< 4.5.
• On stable immunomodulatory treatment for at least 6 months.
• Body mass index (BMI) 18.5-24.9 kg/m².

You may not qualify if:

• Relapse and/or corticosteroid treatment within the last 1 month.
• Clinically significant metabolic, progressive, or malignant disease.
• Use of at least 1 g/day fish oil supplementation.
• Insulin-dependent diabetes mellitus.
• Participation in another interventional study.
• Weight loss or gain ≥ 5% in the last 6 months.
• Following a weight-loss diet in the last 2 months.
• Use of oral anticoagulant therapy.
• Presence of eating disorders, alcohol or substance dependence.
• Pregnancy or breastfeeding.
• Inability to comply with dietary intervention according to weekly follow-up assessments.

Sponsors & Collaborators

• Firat University: lead
• The Scientific and Technological Research Council of Turkey: collaborator

Study Sites (1)

Firat University Hospital, Neurology Clinic

Elâzığ, Elâzığ, 23119, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Fatigue

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Murat Gönen, Prof. Dr.

  Firat University Faculty of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Three-arm, parallel-group randomized controlled trial in adults with relapsing-remitting multiple sclerosis

Study Record Dates

• First Submitted: January 22, 2026
• First Posted: March 30, 2026
• Study Start: March 15, 2024
• Primary Completion: February 10, 2025
• Study Completion: June 20, 2025
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

TU (1)