Propionic Acid for Multiple Sclerosis: Safety and Benefits (Pro-MADAI)

Propionic Acid in Multiple Sclerosis: Safety, Tolerability and Clinical Outcomes From the Pro-MADAI Study

The purpose of this study is to explore the long-term safety, tolerability, and clinical efficacy of propionic acid as an add-on therapy in multiple sclerosis (MS).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Dietary supplement: Propionic acid 1000 mg capsule

Detailed Description

This study is a prospective, open-label extension of the placebo-controlled MADAI trial, including 22 patients with stable relapsing-remitting multiple sclerosis. Participants received oral PA (500 mg twice daily) for an additional 9 months follow-up (FU). Multimodal assessments included cognitive testing (SDMT), physical performance (9HPT, 10mWT), patient-reported outcome measurements PROMs (SF-36, FSMC, ESS, BDI-II), and serum NfL analysis.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Austria
  • State of Salzburg
    • Salzburg, State of Salzburg, Austria, 5020
      • Salzburger Landeskliniken

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of multiple sclerosis (MS)
• Clinically and radiologically stable MS in the previous 3 months
• Age between 18 and 70 years
• Positive finding for oligoclonal bands (OCBs)
• Written consent
• Blood collection at the beginning and end of the study for routine parameter examination as well as sample preservation (especially for measuring propionic acid levels)
• Negative pregnancy test for female participants of childbearing age

Exclusion Criteria:

• History of ongoing propionic acid (PA) supplementation exceeding 3 months
• Positive JC virus titer during natalizumab treatment
• Presence of severe active systemic disease
• Presence of acute neurological conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propionic acid 1000 mg	Dietary supplement: Propionic acid 1000 mg capsule; Patients will receive propionic acid as add on MS treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum neurofilament light chain (NfL)	assessed as pg/ml	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symbol Digit Modalities Test (SDMT)	Measuring cognitive processing speed in patients with MS. Participants are instructed to match symbols to their respective numbers using a reference key. The final score is determined by the number of correct symbol-number pairings completed within 90 seconds. Higher scores indicate better cognitive abilities.	9 months
Nine-Hole Peg Test (9HPT)	Instrument to evaluate fine motor skills of the upper limbs and manual dexterity. Performance is quantified by completion time, with shorter times reflecting better manual dexterity. The participants insert and remove nine small pegs individually into nine corresponding holes on a rectangular board. To improve reliability, this process was repeated twice for each hand.	9 months
10-Meter Walk Test (10mWT)	Evaluation of lower extremity function. Participants were instructed to walk in a straight line at their fastest comfortable pace without running. To avoid measurement bias caused by acceleration and deceleration phases, timing was restricted to the interval between the 2- and 8-meter marks, calculating walking speed over a 6-meter distance.	9 months
Short Form Health Survey (SF-36)	The SF-36 covers eight subscales: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH). These are transformed into two summary scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Both scores are calculated by combining the subscales using specific algorithms. They reflect the overall physical and mental health status, respectively. Each SF-36 domain is scored individually and transformed to a 0-100 scale, where 0 indicates poor health, and 100 represents optimal health. Scores are interpreted as follows: excellent (>60), above average (51-60), average to slightly below average (41-50), moderately below average (31-40), and significant impairment (<30).	9 months
Fatigue Scale for Motor and Cognitive Functions (FSMC)	Fatigue was assessed using the 20-item Fatigue Scale for Motor and Cognitive Functions (FSMC). Motor (FSMCmot) and cognitive (FSMCcog) aspects of fatigue were evaluated separately, and a total score (FSMCtot) was calculated. This score ranges from 20 to 100. Fatigue severity was classified as mild (≥43), moderate (≥53), or severe (≥63).	9 months
Epworth Sleepiness Scale (ESS)	Daytime sleepiness was evaluated using the Epworth sleepiness scale (ESS), an 8-item self-report questionnaire. The ESS assesses the propensity to fall asleep or doze off briefly in different daily situations. Higher scores indicate greater daytime sleepiness. Each Item describes a hypothetical scenario, which participants rate on a 4-point scale (0-3). This results in a total score ranging from 0 to 24 points. Excessive daytime sleepiness was classified as mild (>10), moderate (>13), or severe (>16).	9 months
Beck Depression Inventory-II (BDI-II)	Depressive symptoms were assessed using the Beck Depression Inventory-Second Edition (BDI-II), a 21-item questionnaire. It evaluates various aspects of depression, including libido, fatigue, appetite, decision-making ability, and feelings of guilt. For each item, participants were asked to select one of four statements assessing symptom severity from absent (0) to severe (3).	9 months

Collaborators and Investigators

• Sponsor: Salzburger Landeskliniken

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Actual): May 1, 2025
• Study Completion (Actual): December 12, 2025

Study Registration Dates

• First Submitted: May 3, 2026
• First Submitted That Met QC Criteria: May 12, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Disability; Drug Safety; Cognitive Performance; Propionic Acid
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; propionic acid
• Other Study ID Numbers: 1026/2024-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No