Nicotinamide Riboside Supplementation In Progressive Multiple Sclerosis (Norseman)

Nicotinamide Riboside Supplementation In Progressive Multiple Sclerosis: A Randomised Controlled Trial: The NORSEMAN Study

The purpose of this study is to assess the safety and efficacy of Nicotinamide riboside (NR) for treatment of patients with progressive multiple sclerosis.

The main question it aims to answer is:

• Does NR delay disability progression in progressive multiple sclerosis?

Participants will be treated with NR or placebo for 30 months,

Study Overview

• Status: Recruiting
• Conditions: Progressive Multiple Sclerosis; Multiple Sclerosis
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Nicotinamid riboside

Detailed Description

After being informed about the study and risks, all patients giving written informed consent will undergo a screening period to determine eligibility for study entry.

At baseline patients who meet the eligibility requirements will be randomised in a double- blinded manner (patient and investigator) in a 1:1 ratio to nicotinamide riboside (1000 mg daily) or placebo (once a day)

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Øivind Torkildsen; Phone Number: +4755977039; Email: oivind.fredvik.grytten.torkildsen@helse-bergen.no
• Study Contact Backup: Name: Kjell-Morten Myhr; Phone Number: +47 55976031; Email: kjell-morten.myhr@helse-bergen.no

Study Locations

• Norway
  • Bergen, Norway, 5019
    • Recruiting
    • Haukeland University Hospital
    • Contact: Kjell-Morten Myhr; Phone Number: +4755976031; Email: kjell-morten.myhr@helse-bergen.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A diagnosis of progressive MS (secondary; SPMS or primary; PPMS) according to the 2013 revisions of clinical course of multiple sclerosis and the 2017 revisions of the McDonald criteria.
• Aged 18-65 years.
• EDSS 3-6.5
• Able to perform T25FW test
• The participant must have documented evidence of disability progression observed during the 24 months before screening.
• With or without a stable disease modifying therapy during the last three months.
• Written informed consent for study participation.

Exclusion Criteria:

• A diagnosis of relapsing MS according to the revisions of the McDonald criteria
• Neoplastic disease at baseline
• Previous history of malignant melanoma or breast cancer
• Stable phase of a progressive disease course
• Pregnancy or lactating female patients
• Dementia or other neurodegenerative disorder at baseline visit
• Comorbidity (psychiatric or somatic) that precludes study participation
• Use of high dose vitamin B3 supplementation within 30 days of enrolment
• Genetically confirmed mitochondrial disease or metabolic disorder

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo; Placebo vs study drug	Dietary supplement: Placebo; Placebo tablets
Experimental: Nicotinamid Riboside; Placebo vs study drug	Dietary supplement: Nicotinamid riboside; 500 mg x 2 po

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with sustained disability progression over the treatment period	Defined as an increase in either expanded disability status scale (EDSS), timed 25 foot -walk test (T25W) or 9-hole-peg test. EDSS is measured in scores from 0 - 10. The higher the score the less ambulatory ability. Progression is defined as an increase of >/=1.0 point if baseline EDSS is </= 5.5 or an increase of >/=0.5 point if baseline EDSS is >/= 5.5. Progression in T25WT and 9HPT is defined as an increase of 20% from baseline measures in minutes/seconds.	Baseline to month 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the efficacy of NR compared with placebo, as reflected by EDSS	Proportion of patients with sustained disability progression over the treatment period	Baseline to month 30
To determine the efficacy of NR compared with placebo, as reflected by 25-footwalk	Proportion of patients with sustained disability progression over the treatment period	Baseline to month 30
To determine the efficacy of NR compared with placebo, as reflected by 9-Hole Peg test	Proportion of patients with sustained disability progression over the treatment period	Baseline to month 30
To determine the efficacy of NR compared with placebo, as reflected by total volume of T2 lesions on MRI scans of the brain	MRI	Baseline to month 24
To determine the efficacy of NR compared with placebo, as reflected by formation of lesions	MRI	Baseline to month 24
Changes in brain atrophy in NR-treated patients with primary progressive multiple sclerosis as compared with placebo	MRI	Baseline to month 24
Time to onset of sustained disability progression over the treatment period	Increase in either EDSS, T25FW or 9HPT that is sustained for at least 6 months	Baseline to month 30

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Investigators: Study Director: Kjell-Morten Myhr, Haukeland University hopsital

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: February 22, 2023
• First Posted (Actual): February 23, 2023

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: nicotinamid riboside
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Chronic Disease; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis
• Other Study ID Numbers: 492199

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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