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,

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)

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