Effects of Vitamin B3 in Patients With Ataxia Telangiectasia
Keywords
Abstract
Description
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.
Dates
| Last Verified: | 02/28/2019 |
| First Submitted: | 04/10/2019 |
| Estimated Enrollment Submitted: | 05/21/2019 |
| First Posted: | 05/22/2019 |
| Last Update Submitted: | 05/21/2019 |
| Last Update Posted: | 05/22/2019 |
| Actual Study Start Date: | 03/17/2019 |
| Estimated Primary Completion Date: | 11/30/2019 |
| Estimated Study Completion Date: | 02/29/2020 |
Condition or disease
Intervention/treatment
Dietary Supplement: Intervention group
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Intervention group treatment with vitamin B3 | Dietary Supplement: Intervention group capsules with niagen |
Eligibility Criteria
| Ages Eligible for Study | 2 Years To 2 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | 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. |
Outcome
Primary Outcome Measures
1. Ataxia, SARA (Scale of the assesment and rating of ataxia) [change from baseline -1 month - 4 months - 6 months]
2. Ataxia, ICARS (International Cooperative Ataxia Rating Scale) [change from baseline -1 month - 4 months - 6 months]
3. Ataxia, 9-hole pegboard test. [change from baseline -1 month - 4 months - 6 months]
4. Dysarthria, Radboud dysarthria assesment (RDA) [change from baseline -1 month - 4 months - 6 months]
Secondary Outcome Measures
1. Quality of life questionnaire EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) [change from baseline -1 month - 4 months - 6 months]
2. Laboratory measurements [change from baseline -1 month - 4 months - 6 months]
3. Intelligibility, Intelligibility in Context Scale (ICS) [change from baseline -1 month - 4 months - 6 months]
4. Fatigue, Visual Analogous Scale (VAS) [change from baseline -1 month - 4 months - 6 months]
