Indole-3-PROpionic Acid Clinical Trials - Multiple Sclerosis (iPROACT-MS)

Indole-3-PROpionic Acid Clinical Trials - Multiple Sclerosis (iPROACT-MS)

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsing Remitting Multiple Sclerosis (RRMS)
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Indole-3-propionic acid (IPA)

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Moschoula Passali, MSc, PhD; Phone Number: +45 38633467; Email: moschoula.passali@regionh.dk
• Study Contact Backup: Name: Jette Lautrup Frederiksen, MD, dr.med, professor; Phone Number: +4538633041; Email: jette.lautrup.battistini@regionh.dk

Study Locations

• Denmark
  • Glostrup Municipality, Denmark, 2600
    • Recruiting
    • Glostrup Hospital
    • Contact: Jette Lautrup Frederiksen, MD, dr.med, professor; Phone Number: +45386330; Email: jette.lautrup.battistini@regionh.dk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo capsules	Dietary supplement: Placebo; Two capsules are taken every morning and two capsules are taken every evening for 27 consecutive months. Placebo capsules are taken orally.
Experimental: Indole-3-propionic acid (IPA); IPA capsules	Dietary supplement: Indole-3-propionic acid (IPA); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized relapse rate evaluated at month 27	Defined as the total number of confirmed relapses experienced during the intervention for each patient divided by years of exposure to the intervention and excluding the first three months for both outcome and exposure.	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	New or enlarged brain lesions are evaluated at month 15 and compared to month 3 and at month 27 and compared to month 15; results from unscheduled MRIs between month 3 and month 27 are also considered.	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	Confirmed disability improvement is defined as a reduction in EDSS (expanded disability status scale) score compared to EDSS at month 3 which is of at least 1 point (or 0.5 points if the baseline EDSS >5.5). The EDSS score ranges from 0 to 10 with 0 indicating no neurological disability and 10 indicating death from MS. Measured at month 12 and confirmed at month 15 or measured at month 24 and confirmed at month 27.	The time between month 3 and month 27 after initiation of supplementation.
The time to onset of disability worsening confirmed at 3 months	Confirmed disability worsening is defined as an increase in the EDSS (expanded disability status scale) score compared to EDSS at month 3 which is of at least 1 point (or 0.5 points if the baseline EDSS >5.5). The EDSS score ranges from 0 to 10 with 0 indicating no neurological disability and 10 indicating death from MS. 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.
Cumulative change in EDSS score	Calculated as area under the curve (AUC) for measured values of the EDSS (expanded disability status scale) score from month 3 to month 24. The EDSS score ranges from 0 to 10 with 0 indicating no neurological disability and 10 indicating death from MS.	The time between month 3 and month 24 after initiation of supplementation.
Multiple Sclerosis Functional Composite (MSFC)	A composite score used to assess neurological function by combining results from the Timed 25-Foot Walk (T25FW) test, the Nine-Hole Peg Test (9HPT) and the Symbol Digit Modalities Test (SDMT) evaluated at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Symbol Digit Modalities Test (SDMT)	A measure of cognitive function and especially processing speed - evaluated at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
California Verbal Learning Test-II (CVLT-II)	A measure of verbal learning and memory - evaluated at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Brief Visuospatial Memory Test - Revised (BVMR-R)	A measure of visuospatial memory - evaluated at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Intra-eye change in peripapillary retinal nerve fiber layer (RNFL) thickness	Measured using Optical Coherence Tomography (OCT) at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Intra-eye change in ganglion cell and inner plexiform layer (GCIPL) thickness	Measured using Optical Coherence Tomography (OCT) at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Modified Fatigue Impact Scale (MFIS-21)	The MFIS-21 consists of a physical subscale (ranges from 0-36), a cognitive subscale (ranges from 0-40) and a psychosocial subscale (ranges from 0-8). The total MFIS-21 scale is computed by adding the scores from the physical, the cognitive and the psychosocial subscales. It ranges from 0-84 with higher scores indicating a greater impact from fatigue. MFIS-21 is evaluated longitudinally at months 0, 3, 6, 9, 12, 15, 18, 21, 24 and 27.	The time between month 0 and month 24 after initiation of supplementation.
Multiple Sclerosis Quality of Life-54 (MSQOL-54)	The MSQOL-54 questionnaire is used to calculate a physical health composite score and a mental health composite score. They both range from 0-100 with higher scores indicating better health/ higher quality of life. The questionnaire is administered at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Brain-derived neurotrophic factor (BDNF)	Brain-derived neurotrophic factor measured in platelet-free plasma samples using ELISA or mesoscale. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
C-reactive protein (CRP)	CRP measured in plasma (mg/L) as a biomarker of infection and systemic inflammation. Lower-limit of quantification: 0,4 mg/L. Values below 0,4 mg/L are imputed as 0,2 mg/L. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Triglycerides	Plasma triglycerides (mmol/l) monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Non-HDL cholesterol	Non-HDL cholesterol calculated as total cholesterol minus HDL cholesterol (mmol/l). Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
C-peptide	Proinsulin C-peptide (pmol/l) measured in plasma. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Fasting glucose	Plasma glucose (mmol/l). Participants abstain from eating and drinking after 22.00 the day before. Only water is allowed. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
8-iso-prostaglandin F2α and other F2-isoprostanes	F2-isoprostanes with a specific focus on 8-iso-prostaglandin F2α measured in morningurine or blood samples as a marker of oxidative stress-related lipid oxidation. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
8-oxo-dG	8-oxo-dG (8-Oxo-2'-deoxyguanosine) measured in blood or morningurine samples as a marker of oxidative stress-related DNA damage. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Fecal lipocalin	Lipocalin measured in fecal samples as a sensitive biomarker of intestinal inflammation. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Microbiota profiling of fecal samples	Microbiota profiling of fecal samples using molecular biology methods including but not limited to sequencing and flowcytometric analyses. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Serum and fecal metabolomics	Targetted and untargetted liquid-chromatography mass-spectrometry-based metabolomics to measure diet-, host- and microbial-derived metabolites. Targetted analyses aim to quantify indole-3-propionic acid and its metabolites (biomarker of compliance as well as absorptive and metabolic capacity), other bacterial- and host metabolites of tryptophan as well as short-chain fatty acids. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with progression independent of relapse and/or MRI activity	Tertiary efficacy outcome related to multiple sclerosis. Progression is defined as an increase in the EDSS score compared to the EDSS at month 3 which is of at least 1 point (or 0.5 points if the baseline EDSS >5.5). The EDSS score ranges from 0 to 10 with 0 indicating no neurological disability and 10 indicating death from MS. Measured at month 12 and confirmed at month 15 or measured at month 24 and confirmed at month 27.	The time between month 3 and month 24 after initiation of supplementation.
Six Spot Step Test (SSST)	Tertiary efficacy outcome related to multiple sclerosis. A measure of walking ability, including speed, co-ordination and balance - evaluated at month 0, month 12 and month 24.	The time between month 0 and month 24 after initiation of supplementation.
Nine-Hole Peg Test (9-HPT)	Tertiary efficacy outcome related to multiple sclerosis. A measure of finger dexterity - evaluated at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Glial Fibrillary Acidic Protein (GFAP)	Tertiary efficacy outcome related to multiple sclerosis. Monitored longitudinally in serum samples at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Chitinase 3 Like 1 (CHI3L1)	Tertiary efficacy outcome related to multiple sclerosis. Monitored longitudinally in serum samples at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Chitotriosidase 1 (CHIT1)	Tertiary efficacy outcome related to multiple sclerosis. Measured longitudinally in serum samples at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Work Productivity and Activity Impairment (WPAI) questionnaire	Tertiary efficacy outcome related to multiple sclerosis. WPAI results are expressed as impairment percentages where higher percentages indicate greater impairment and lower productivity. Evaluated at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Glycated hemoglobin (HbA1c)	Exploratory outcome related to metabolic health. HbA1c (IFCC, mmol/mol) measured in whole blood. Estimated average glucose values (mmol/l) are also calculated automatically from HbA1c by our laboratory. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Total cholesterol	Exploratory outcome related to metabolic health. Plasma cholesterol (mmol/l). Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
HDL cholesterol	Exploratory outcome related to metabolic health. Plasma high-density lipoprotein (HDL) (mmol/l). Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
LDL cholesterol	Exploratory outcome related to metabolic health. Plasma low-density lipoprotein (LDL) (mmol/l). Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
VLDL cholesterol	Exploratory outcome related to metabolic health. Plasma very low-density lipoproteins (mmol/l). Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Body mass index (BMI)	Exploratory outcome related to metabolic health. BMI calculated as weight (kg)/ height (m)^2. Monitored longitudinally at months 0, 12, and 24. Height is only measured at baseline with longitudinal changes in BMI reflecting changes in weight.	The time between month 0 and month 24 after initiation of supplementation.
Sagittal abdominal diameter (SAD)	Exploratory outcome related to metabolic health. The distance (cm) from the lower back to the highest point of the abdomen while in a supine position as a measure of visceral obesity. Monitored longitudinally at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Waist circumference	Exploratory outcome related to metabolic health. Calculated as an average of two measurements and expressed in cm. Monitored longitudinally at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Hip circumference	Exploratory outcome related to metabolic health. Calculated as an average of two measurements and expressed in cm. Monitored longitudinally at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Waist-to-Hip ratio	Exploratory outcome related to metabolic health. Monitored longitudinally at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Blood pressure	Exploratory outcome related to metabolic health. Blood pressure (mm Hg) defined as the lowest value obtained across three measurements. Monitored longitudinally at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Resting heart rate	Exploratory outcome related to metabolic health. Resting heart rate defined as the lowest value obtained across three measurements while sitting in a relaxed position. Monitored longitudinally at month 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Flowcytometric analyses of microvesicles and endothelial progenitor cells	Exploratory outcome related to systemic inflammation. Monitored longitudinally in platelet-free plasma at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Circulating cytokines and acute phase reactants	Exploratory outcome related to systemic inflammation. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Serum antibodies	Exploratory outcome related to systemic inflammation. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Urinary neopterin	Exploratory outcome related to systemic inflammation. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
suPAR	Exploratory outcome related to systemic inflammation. Soluble urokinase plasminogen activator receptor (suPAR) monitored longitudinally in blood samples at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Osteopontin	Exploratory outcome related to systemic inflammation. Monitored longitudinally in blood samples at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Buffycoat gene expression analyses	Exploratory outcome related to systemic inflammation. Gene expression analyses monitored longitudinally in buffycoat samples collected at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Protein carbonyls	Exploratory outcome related to oxidative stress. Protein carbonyls measured in blood or morningurine samples as a marker of protein oxidation. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Malondialdehyde	Exploratory outcome related to oxidative stress. Malondialdehyde monitored longitudinally in blood or morningurine samples at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Glial cell line-derived neurotrophic factor (GDNF)	Exploratory outcome monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Platelet-derived growth factor (PDGF)	Exploratory outcome monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Gastrointestinal comfort and bowel movement pattern	Exploratory outcome related to gastrointestinal function. Self-reported (questionnaire) gastrointestinal symptoms of bloating, pain, rumbling, flatulence, constipation, hard stools and diarrhea evaluated using a visual analogue scale as well as a question on the frequency of defecation. Monitored longitudinally at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Stool consistency	Exploratory outcome related to gastrointestinal function. Classification of stool consistency using the Bristol Stool Chart. Numerical scale ranging from 1 (separate hard lumps) to 7 (liquid consistency with no solid pieces) with one-unit increments. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Gastrointestinal transit time	Exploratory outcome related to gastrointestinal function. Measurement of transit time through the digestive system using a so-called maize test. Participants consume 100 grams of sweet maize in the morning between 5.30-10.00 while still in a fasting state. The exact date and time of consumption is registered and so is the exact date and time when maize is observed for the first time in feces. Transit time is expressed as the difference between the ingestion and fecal excretion timepoints in hours. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Antibody-coating of fecal microbes	Exploratory outcome related to gastrointestinal function. Evaluation of endogenous antibody-coating of fecal microbes (bacteria, viruses etc) as well as the ability of fecal microbes to be bound by disease-related and other antibodies. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Fecal pH	Exploratory outcome related to gastrointestinal function. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Bacterial polysaccharides	Exploratory outcome related to gastrointestinal function. Lipopolysaccharide (LPS, endotoxin) and LPS-binding protein, capsular polysaccharides or other bacterial polysaccharides measured in blood samples as a biomarker of bacterial translocation across the intestinal epithelium. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Intestinal fatty acid binding protein	Exploratory outcome related to gastrointestinal function. Measurements of intestinal fatty acid binding protein in blood samples as a biomarker of enterocyte damage. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Pre-haptoglobin 2	Exploratory outcome related to gastrointestinal function. Measurement of pre-haptoglobin 2 in blood samples as a biomarker of intestinal permeability. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Citrulline	Exploratory outcome related to gastrointestinal function. Measurement of citrulline in blood samples as a biomarker of intestinal function. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Calprotectin	Exploratory outcome related to gastrointestinal function. Calprotectin measured in fecal samples as a biomarker of intestinal inflammation. Monitored longitudinally at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Questionnaire-based self-reporting of experienced effects	A safety outcome. Study participants are asked whether they have experienced any positive or negative effects and whether they believe they have been given IPA or placebo. Evaluated at months 3, 12, 15, 24 and 27.	The time between month 3 and month 27 after initiation of supplementation.
Registration of side effects	A safety outcome. Interviews with the aim of uncovering any side effects or adverse events. Results are registered using the REDCap instrument "CDISC|CDASHIG v2.1|Adverse Events". Evaluated at months 3, 12, 15, 24 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Leucocyte counts	A safety outcome. Total leucocytes, basophils, eosinophils, lymphocytes, monocytes, neutrophils as well as the joint group of metamyelo-, myelo- and promyelocytes. All counted in whole blood samples (x10^9/l). Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Thrombocytes	A safety outcome. Thrombocytes measured in whole blood (x 10^9/L). Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Hemoglobin	A safety outcome. Hemoglobin measured in whole blood (mmol/l). Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Alanine transaminase (ALT)	A safety outcome. Plasma alanine transaminase (ALT, U/l) measured as a biomarker of liver function. Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Aspartate aminotransferase (AST)	A safety outcome. Plasma aspartate aminotransferase (U/l) also known as aspartate transaminase measured as a biomarker of liver and muscle damage. Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Lactate dehydrogenase (LDH)	A safety outcome. Lactate dehydrogenase measured in plasma (U/l). Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Bilirubin	A safety outcome. Bilirubins measured in plasma (µmol/L) as a biomarker of liver function. Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Alkaline phosphatase	A safety outcome. Alkaline phosphatase (U/l) as a biomarker of liver function. Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Thyroid-stimulating hormone (TSH)	A safety outcome. Thyroid-stimulating hormone measured in plasma (mU/L) as a biomarker of thyroid function. Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Thyroxine (T4)	A safety outcome. Monitored in blood samples as a biomarker of thyroid function at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Triiodothyronine (T3)	A safety outcome. Monitored in blood samples as a biomarker of thyroid function at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Albumin	A safety outcome. Albumin measured in plasma (g/L). Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Coagulation factors II, VII and X (international normalized ratio (INR))	A safety outcome. Coagulation factors II, VII and X (INR) measured in citrate plasma as a biomarker of coagulation. Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Creatinine	A safety outcome. Plasma creatinine (µmol/L) as a biomarker of kidney function. Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Estimated glomerular filtration rate (eGFR)	A safety outcome. Estimated glomerular filtration rate (eGFR/ 1,73m² (ml/min)) as a biomarker of kidney function. Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Counting of leftover capsules	A measure of compliance. Evaluated longitudinally at months 3, 12, 15, 24 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Questionnaire regarding demographic characteristics, socioeconomic background, lifestyle factors, and other potential confounding factors	Information on potential confounders or effect modifiers. The questionnaire is administered at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Food frequency questionnaire	Information on potential confounders or effect modifiers. A food frequency questionnaire (FFQ) regarding dietary habits and food consumption during the past year is administered at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Objective biomarkers of dietary intake	Information on potential confounders or effect modifiers. Measurement of fatty acids, vitamins, minerals, amino acids and food-derived DNA in blood, urine and fecal samples. Monitored at months 0, 3, 15 and 27.	The time between month 0 and month 27 after initiation of supplementation.
Major Depression Inventory (MDI)	Information on potential confounders or effect modifiers. The Major Depression Inventory (MDI) score ranges from 0 to 50 with higher scores suggesting higher degrees of depression. Evaluated at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.
Pittsburgh Sleep Quality Index (PSQI)	Information on potential confounders or effect modifiers. The global Pittsburgh Sleep Quality Index (PSQI) score is calculated. It ranges from 0 to 21 with higher scores indicating worse sleep quality. Evaluated at months 0, 12 and 24.	The time between month 0 and month 24 after initiation of supplementation.

Collaborators and Investigators

• Sponsor: Glostrup University Hospital, Copenhagen
• Collaborators: University of Copenhagen; University of Southampton
• Investigators: Principal Investigator: Jette Lautrup Frederiksen, MD, dr.med, professor, Copenhagen University Hospital, Rigshospitalet-Glostrup

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2026
• Primary Completion (Estimated): July 15, 2028
• Study Completion (Estimated): July 15, 2028

Study Registration Dates

• First Submitted: November 23, 2025
• First Submitted That Met QC Criteria: December 24, 2025
• First Posted (Actual): January 5, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: multiple sclerosis; dietary supplement; gut-brain axis; gut bacterial metabolite; indole-3-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; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: H-25042489

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in published articles, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following publication of the article they are presented in.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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