Indole-3-PROpionic Acid Clinical Trials - Multiple Sclerosis

NCT07318129 | Recruiting

• 1 other identifier: H-25042489
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

This study, iPROACT-MS, is part of the iPROACT group of clinical trials aiming to investigate the effects of oral supplementation with indole-3-propionic acid (IPA) in humans. IPA is naturally produced as a gut bacterial metabolite with the amino acid tryptophan as substrate. The primary aim of iPROACT-MS is to investigate whether patients with relapsing-remitting multiple sclerosis (RRMS) can benefit from supplementation with IPA. The hypothesis is that supplementation with IPA will protect against MS-related disease activity, neurodegeneration and metabolic abnormalities. Secondary, iPROACT-MS aims at elucidating the complex relationships between lifestyle, gut microbial factors, inflammation, oxidative stress, metabolic health, MS disease severity and MS disease activity.

Conditions

Relapsing Remitting Multiple Sclerosis (RRMS)

Keywords

indole-3-propionic acid; multiple sclerosis; gut bacterial metabolite; dietary supplement; gut-brain axis

Outcome Measures

Primary Outcomes (1)

• No evidence of disease activity (NEDA)

  The percentage of patients that maintain no evidence of disease activity (NEDA-3) in the time between month 3 and month 27 after initiation of supplementation. NEDA-3 is defined as a binary composite consisting of absence of confirmed relapses, no new or enlarged lesions on brain MRI and no confirmed disability progression. For relapses to be confirmed, they need to be accompanied by an increase of at least 0.5 points on the EDSS or 2 points in one of the EDSS functional system scores, or at least 1 point in two or more of the EDSS functional system scores. Confirmed disability progression is defined as an increase in the EDSS score compared to EDSS at month 3 which is of at least 1 point (or 0.5 points if the baseline EDSS \>5.5) and is sustained for three months (measured at month 12 and confirmed at month 15 or measured at month 24 and confirmed at month 27 or measured at a relapse evaluation prior to or at month 24 and confirmed at the next visit or the latest at month 27).

  The time between month 3 and month 27 after initiation of supplementation.

Secondary Outcomes (25)

• Annualized relapse rate evaluated at month 27

  The time between month 3 and month 27 after initiation of supplementation.

• Total (cumulative) number of new or enlarged T2-weighted/FLAIR brain lesions per scheduled yearly MRI evaluated at month 27

  The time between month 3 and month 27 after initiation of supplementation.

• Serum neurofilament light chain (sNfL)

  Evaluated longitudinally at months 0, 3, 15 and 27.

• Percentage of patients with disability improvement confirmed at 3 months

  The time between month 3 and month 27 after initiation of supplementation.

• The time to onset of disability worsening confirmed at 3 months

  The time between month 3 and month 27 after initiation of supplementation.

Other Outcomes (63)

• Percentage of patients with progression independent of relapse and/or MRI activity

  The time between month 3 and month 24 after initiation of supplementation.

• Six Spot Step Test (SSST)

  The time between month 0 and month 24 after initiation of supplementation.

• Nine-Hole Peg Test (9-HPT)

  The time between month 0 and month 24 after initiation of supplementation.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo capsules

Dietary Supplement: Placebo

Indole-3-propionic acid (IPA)

EXPERIMENTAL

IPA capsules

Dietary Supplement: Indole-3-propionic acid (IPA)

Interventions

Placebo DIETARY_SUPPLEMENT

Two capsules are taken every morning and two capsules are taken every evening for 27 consecutive months. Placebo capsules are taken orally.

Placebo

Indole-3-propionic acid (IPA) DIETARY_SUPPLEMENT

Two capsules are taken every morning and two capsules are taken every evening for 27 consecutive months. Active capsules are taken orally and contain 250 mg of IPA each resulting in a total daily dose of 1000 mg of IPA.

Indole-3-propionic acid (IPA)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women and men ≥18 and ≤65 years of age
• Diagnosed with RRMS according to the 2017 McDonald criteria (or newer updates)
• Routinely treated and monitored for MS
• Speak and read Danish
• Deemed physically and mentally able to participate in this study

You may not qualify if:

• Active malignancy
• Diagnosis of Crohn's disease and ulcerative colitis
• Other comorbidities deemed to be relevant
• Haematopoietic stem cell transplantation
• Current or past treatment with non-MS related treatments deemed to be relevant
• Pregnancy or lactation
• People with MR contraindications:
• Severe claustrophobia
• Incompatible implants/ foreign objects, including implanted pacemakers, heart valve prostheses, prostheses in the middle ear, implanted devices (e.g., insulin pump), metal debris, e.g., metal splinters in the eyes, miscellaneous shunts and catheters, metal clips from operations

Sponsors & Collaborators

• Glostrup University Hospital, Copenhagen: lead
• University of Copenhagen: collaborator
• University of Southampton: collaborator

Study Sites (1)

Glostrup Hospital

Glostrup Municipality, 2600, Denmark

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Jette Lautrup Frederiksen, MD, dr.med, professor

  Copenhagen University Hospital, Rigshospitalet-Glostrup

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jette Lautrup Frederiksen, MD, dr.med, professor

CONTACT

+4538633041; jette.lautrup.battistini@regionh.dk

Moschoula Passali, MSc, PhD

CONTACT

+45 38633467; moschoula.passali@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Each set of capsule containers (the containers to be used by a study participant during the intervention) is labelled with a unique ID and no other identifier. A randomization key is prepared by an external party randomizing study participants to IPA or placebo using stratified block randomization with random block sizes of 4 or 6. Stratification accounts for recent evidence of disease activity (yes vs. no) defined as experience of clinical relapses within the past year or demonstration of new, contrast-enhanced or enlarged lesions on a clinical MRI scan performed within the last 12 months from randomization. A software system is used to reveal the unique container ID to be used by each randomized participant without revealing its corresponding arm. Only after all study participants have completed the trial and the collected data have been cleaned and quality checked, are the researchers performing the statistical analyses informed about which participants belong to each arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, dr.med, professor at DMSc

Study Record Dates

• First Submitted: November 23, 2025
• First Posted: January 5, 2026
• Study Start: January 26, 2026
• Primary Completion (Estimated): July 15, 2028
• Study Completion (Estimated): July 15, 2028
• Last Updated: January 28, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following publication of the article they are presented in.
• Access Criteria: Researchers who provide a methodologically sound proposal can access the IPD to achieve the aims of the approved proposal. Proposals should be directed to jette.lautrup.battistini@regionh.dk. To gain access, data requestors will need to sign a data access agreement. Data and explanatory files will be made available at a third party website.

Locations

DK (1)