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CompletedNCT07595081Pro-MADAIUpdated Sep 22, 2026

Propionic Acid for Multiple Sclerosis: Safety and Benefits

An interventional study of Propionic acid 1000 mg capsule in Multiple Sclerosis, sponsored by Salzburger Landeskliniken. Completed at 1 site in Austria. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-09-22.

Sponsored by Salzburger Landeskliniken · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
22
Allocation
Non-randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

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).

Read the 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 safety and tolerability, cognitive testing (SDMT), physical performance (9HPT, 10mWT), and patient-reported outcome measurements PROMs (SF-36, FSMC, ESS, BDI-II).

02

Conditions studied

  • Multiple Sclerosis

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Keywords

  • Multiple Sclerosis
  • Propionic Acid
  • Drug Safety
  • Cognitive Performance
  • Disability
03

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
22 participants (actual)

Study arms

  • Active comparator
    Propionic acid 1000 mg

    Participants recruited from the MADAI trial receive oral PA 500 mg twice daily for an additional 9-month follow-up period.

    Dietary Supplement: Propionic acid 1000 mg capsule

  • No intervention
    Observational control cohort

    Participants who received no further PA supplementation are identified through routine clinical follow-up after completion of the MADAI trial.

Interventions

  • Dietary supplementPropionic acid 1000 mg capsule

    Patients will receive propionic acid as add on MS treatment.

05

What researchers measure

Primary outcomes

  1. Safety and tolerability

    Treatment-Emergent Adverse Events Number of participants experiencing at least one treatment-emergent adverse event during the study, as assessed through participant reports, patient diaries, and routine laboratory assessments.

    Time frame: 9 months

Secondary outcomes

  1. 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.

    Time frame: 9 months

  2. 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.

    Time frame: 9 months

  3. 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.

    Time frame: 9 months

  4. 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).

    Time frame: 9 months

  5. 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).

    Time frame: 9 months

  6. 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).

    Time frame: 9 months

  7. 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).

    Time frame: 9 months

06

Study locations

1 site
  • Salzburger Landeskliniken
    Salzburg, State of Salzburg 5020, Austria
07

References and documents

Publications

  • Moser T, Hitzl W, Lerda-Casaccia T, Unterhofer M, Demjaha R, Martinez-Serrat M, Khalil M, Harrer A, Bohm B, Hofbauer P, Cadamuro J, Huber-Schonauer U, Trinka E, Wipfler P. Propionic acid in multiple sclerosis: a phase 2b, double-blind, randomized placebo-controlled trial. Brain. 2026 Jul 6;149(7):2286-94. doi: 10.1093/brain/awag099. Online ahead of print. PubMed 42402345 ↗
08

Registry details

Key details

Study ID
NCT07595081
Lead sponsor
Salzburger Landeskliniken
Responsible party
Tobias Moser (Principal Investigator, Salzburger Landeskliniken) — Principal investigator
First posted
May 19, 2026
Start date
Aug 1, 2024
Primary completion
May 1, 2025
Completion
Dec 12, 2025
Last update
Sep 22, 2026

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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