Effects of Vitamin B3 in Patients With Ataxia Telangiectasia

Study Overview
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Brief Summary
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This clinical trial investigates the effects of nicotinamide riboside (vitamin B3) on the disease course of patients with ataxia telangiectasia. Patients will be treated during four consecutive months with nicotinamide riboside (25mg/kg/day), followed by a washout period of two months. Main study parameters/endpoints: Ataxia, dysarthria, quality of life, laboratory parameters.

Detailed Description
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Rationale: Ataxia Telangiectasia (A-T) is an autosomal recessively inherited neurodegenerative disorder, with a high cancer risk, that also affects the immune and respiratory system. Therapy for A-T is restricted to symptomatic treatment including rehabilitation care, combined with infection prevention and treatment, and screening for pulmonary dysfunction and malignancies. A-T is caused by mutations in the ATM gene. The ATM protein plays a pivotal role in more than 100 different biochemical processes, among which cellular energy metabolism, cell signaling, and DNA repair. Nicotinamide adenine dinucleotide (NAD+) is an essential molecule in many of these processes and studies have shown that NAD+ deficiency plays a role in disease mechanisms underlying DNA repair disorders such as A-T. NAD+ is available in food, but can also be synthesized in the body from its precursors nicotinamide, nicotinic acid, and nicotinamide riboside (NR), as a group called vitamin B3. Treatment of experimental A-T animal models with NR showed beneficial effects. The aim of this study is to investigate whether treatment with NR during a period of six months may have positive effects on the disease course of patients with A-T. Objective: To investigate the effects of NR on the disease course of patients with ataxia telangiectasia. Study design: Single center, interventional, explorative, open-label proof of concept study. Study population: Patients with A-T (age >2 years). Intervention (if applicable): Patients will be treated with nicotinamide riboside (25mg/kg/day), during four consecutive months, followed by a washout period of two months. Main study parameters/endpoints: Ataxia, dysarthria, quality of life, laboratory parameters.

Official Title
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Effects of Nicotinamide Riboside (Vitamin B3) in Patients With Ataxia Telangiectasia.

Conditions
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Ataxia Telangiectasia, ATM Gene Mutation

Intervention / Treatment
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* Dietary Supplement: Vitamin B3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A-T patients who visit our outpatient clinic. Genetically confirmed diagnosis of A-T by the identification of pathogenic mutations of the ATM gene. Age ≥ 2 years or older and bodyweight ≥ 12 Kg. Informed consent. Exclusion Criteria: Additional medical condition or illness that impair the patient's ability to participate in the study (e.g. actual treatment of a malignancy, active infection, poorly controlled diabetes mellitus, hypertension, organ failure, clinically significant hematological or biochemical abnormalities different from the usual abnormalities in A-T) Elevated serum transaminases (> 2 times upper limit of normal) Participation in another interventional study at start of the study or during the study Pregnancy. Breast feeding.

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label proof of concept study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>treatment with vitamin B3 | Dietary Supplement: Vitamin B3<br>* capsules with niagen<br>* Other names: Nicotinamide riboside;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ataxia, SARA (Scale of the assesment and rating of ataxia) | Changes in the total score will be measured. | change from baseline -1 month - 4 months - 6 months | 
| Ataxia, ICARS (International Cooperative Ataxia Rating Scale) | Changes in the total score will be measured. | change from baseline -1 month - 4 months - 6 months | 
| Ataxia, 9-hole pegboard test. | Changes in fastes time of the 9-hole pegboard test will be measured. | change from baseline -1 month - 4 months - 6 months | 
| Dysarthria, Radboud dysarthria assesment (RDA) | Changes in maximum performance tasks and severity of dysarthria will be measured. | change from baseline -1 month - 4 months - 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life questionnaire EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) | Changes in the total quality of life score will be measured. | change from baseline -1 month - 4 months - 6 months | 
| Laboratory measurements | Results will be summarized descriptively, with abnormal and clinically notable values/findings being identified | change from baseline -1 month - 4 months - 6 months | 
| Intelligibility, Intelligibility in Context Scale (ICS) | Changes in the total score of the Intelligibility in Context Scale (ICS), will be measured. | change from baseline -1 month - 4 months - 6 months | 
| Fatigue, Visual Analogous Scale (VAS) | Changes in the total VAS score will be measured. | change from baseline -1 month - 4 months - 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ataxia Telangiectasia, ATM Gene Mutation, ATM protein, Nicotinamide riboside