NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia

Study Overview
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Brief Summary
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The study investigates the effect of dietary supplementation of nicotinamide ribonucleoside (NR) in children with ataxia telangiectasia (AT), with main focus on neurological symptoms.

Detailed Description
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Ataxia Telangiectasia (AT) is a genetic disease, where patients are born with mutations in the Ataxia- Telangiectasia Mutated (ATM) gene. The gene codes for the ATM kinase, which is required for repair of DNA double-stranded breaks and DNA damage response signalling. There is no treatment available for the neurological manifestations of AT. The study investigates the effects of NR (300 mg/day) during 2 years.

Official Title
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NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia

Conditions
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Ataxia Telangiectasia

Intervention / Treatment
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* Drug: Nicotinamide ribonucleoside


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinically and molecular verified classical A-T disease Exclusion Criteria: less than 2 years of age participation in other on-going study pregnancy liver failure other severe medical conditions considered to set patient at risk

Ages Eligible for Study
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Minimum Age: 3 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NR treated<br>Nicotinamide ribonuceloside (NR), sold under the trade name Niagen™ | Drug: Nicotinamide ribonucleoside<br>* Two year intervention<br>* Other names: Niagen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NAD metabolome | Increase of NAD+ and other stable NAD+ metabolites (referred to as the NAD metabolome) in blood | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient well being | Improved or stabilized health-related quality of life (HRQOL) measured with the Pediatric Quality of Life Inventory (PedSQL) | 2 years | 
| Motoric function - The Scale for the Assessment and Rating of Ataxia (SARA) | Stabilized motoric function measured with SARA. The SARA scale is made up of measurements related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test. The range is from no ataxia (value 0) to severe ataxia (value 40). | 2 years | 
| Motoric function - The International Cooperative Ataxia Rating Scale (ICARS) | Stabilized motoric function measured with ICARS. The ICARS scale is made from measurements of postural and gait disturbances, limb ataxia, dysarthria, and oculomotor disorders. The range is from no ataxia (value 0) to severe ataxia (value 100). | 2 years | 
| Motoric function - Customized gait scale (GS) | Stabilized motoric function measured with GS. The gait scale assess gait functionality in patients with Ataxia-telangiectasia. The range is from no walking ability (value 0) to normal walking ability according to age and maturity (value 10). | 2 years | 
| Motoric function - AT Neuro Examination Scale Toolkit, updated version (AT-NEST) | Stabilized motoric function measured with AT-NEST. The AT-NEST scale is made from scoring of speech, handwriting/drawing, oculomotor, ataxia, muscle strength, neuropathy, growth, nutrition, learning ability/cognition, MS mental state. The range is from normal (value 144) to severe ataxia (value 0). | 2 years | 
| Motoric function - Clinical Global Scale rating instrument for A-T | Stabilized motoric function measured with Clinical Global Scale rating instrument for A-T. The Clinical Global Scale rating instrument for A-T scale is made from scoring of gait ataxia, dysmetria, dysarthria, extrapyramidal movements and eye movements. The range is from normal (value 0) to severe (value 4). | 2 years | 
| Liver function | Normalized or stabilized liver function as assessed by blood levels of -alfa fetoprotein (AFP) | 2 years | 
| Blood sugar control | Normalized or stabilized blood sugar levels as measured in blood: -HbA1c | 2 years | 
| Mitochondrial function | Normalized or stabilized mitochondrial markers in blood: lactate lactate dehydrogenase FGF21 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ataxia telangiectasia, nicotinamide ribonucleoside, Louis-Bar syndrome