Nicotinamide Riboside Supplementation In Progressive Multiple Sclerosis

Study Overview
=================
Brief Summary
-----------------
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,

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)

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

Conditions
-----------------
Multiple Sclerosis, Progressive Multiple Sclerosis

Intervention / Treatment
-----------------
* Dietary Supplement: Nicotinamid riboside
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomised placebo-controlled trial. Experimental: Placebo Placebo vs study drug (Nicotinamid riboside 500 mg x 2 po)
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo<br>Placebo vs study drug | Dietary Supplement: Placebo<br>* Placebo tablets<br>|
| Experimental: Nicotinamid Riboside<br>Placebo vs study drug | Dietary Supplement: Nicotinamid riboside<br>* 500 mg x 2 po<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nicotinamid riboside