Ataxia-telangiectasia: Treating Mitochondrial Dysfunction With Nicotinamide Riboside

NCT06324877 | Not Yet Recruiting DMC

• 1 other identifier: HREC/24/QCHQ/106030
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Study design: Single arm open-label clinical trial in ataxia-telangiectasia to test the effects of nicotinamide riboside on ataxia scales, immune function, and neurofilament light chain. Study population: 6-10 patients with Ataxia-Telangiectasia. Dose: Nicotinamide riboside 25 mg/kg/day in 3 equal divided doses. Primary endpoint: Scales for assessment and rating of ataxia (SARA), and International Cooperative Ataxia Rating Scale (ICARS). Improvement of at least ½ standard deviation in key clinical scales which includes either; a) significant improvement in total combined scores from the SARA and ICARS scales, and /or b) significant improvements any aspects of the SARA and ICARS scales individually, especially pertaining to; Postural and gait improvements, Improved syllable speed and articulation, Improved fine motor skills. Secondary endpoints: Serum analysis of neurofilament light chain (Nfl), Type 1 Interferon (INFs) epigenetic signature

Conditions

Ataxia Telangiectasia

Keywords

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Spinocerebellar Ataxias; Neurocutaneous Syndromes; Genetic Diseases, Inborn; Primary Immunodeficiency Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Ataxia; Cerebellar Ataxia; Ataxia Telangiectasia; Telangiectasis

Outcome Measures

Primary Outcomes (2)

• Scales for assessment and rating of ataxia

  Scales for assessment and rating of ataxia is a validated cerebellar ataxia tool, measuring gait (scale 0-8), stance (scale 0-6), sitting (scale 0-4), speech (scale 0-6), finger-chase test scale 0-4), finger nose-test (scale 0-4), fast alternating movements (scale 0-4) and heel-shin test (scale 0-4). 0 indicates normal function, escalating numbers in the scale domains indicate increased difficultly with the measured tasks.

  4 monthly assessment over 12 months

• International Cooperative Ataxia Rating Scale

  International Cooperative Ataxia Rating Scale is a scale recorded out of 100 with 19 items and 4 sub-scales and has been used in A-T. 0 indicates normal function, escalating numbers in the scale domains indicate increased difficulty with the measured tasks.

  4 monthly assessment over 12 months

Secondary Outcomes (2)

• Serum analysis of neurofilament light chain

  12 months

• Type 1 Interferon epigenetic signature

  12 months

Other Outcomes (1)

• Quality of Life Measures

  4 monthly assessment over 12 months

Study Arms (1)

Single arm (full group)

OTHER

Single arm, open-label. Dose will be via oral capsule supplementation Nicotinamide Riboside at 25mg/kg/day divided into 3 doses (max 300mgs 3 times per day). Dosing will occur via 3 equal doses 3 times a day for 12 months.

Drug: Nicotinamide riboside

Interventions

Nicotinamide riboside DRUG

Oral capsule Nicotinamide Riboside 25mg/kg/day divided into 3 equal doses

Single arm (full group)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who meet all of the following criteria are eligible for enrolment:
• Patients of either sex, of any age, with a confirmed diagnosis of A-T,
• Patients who are able to undertake the study procedures,
• Families who are able to comply with the protocol for its duration and who provide informed patient assent and consent signed and dated by parent/legal guardian or adult participant according to local regulations.

You may not qualify if:

• Participants who meet any of these criteria are not eligible for enrolment:
• Patients whose parents/legal guardians are not able to provide consent
• Patients who have been in another randomised clinical intervention trial where the use of investigational medicinal product within 3 months or 5 half-lives, whichever is longer, before study enrolment
• Taking off label mediations or nutritional supplements that the PI consider would impact participant's safe participation.
• Patients who are pregnant and/or lactating, planning a pregnancy during the study. Contraception must be used for sexually active male and female participants
• Liver enzymes (alanine aminotransferase \[ALT\]/aspartate aminotransferase \[AST\]) or total bilirubin \> 2 x the upper limit of normal at the time of screening.
• Renal insufficiency as defined by estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m2 at the screening visit.
• Any comorbid medical condition that in the assessment of the PI that would impact participant's safe participation (e.g. active cancer requiring treatment)
• Evidence of dysphagia that places subject at risk of aspiration if orally fed.

Sponsors & Collaborators

• The University of Queensland: lead

Study Sites (1)

Queensland Children's Hospital

Brisbane, Queensland, 4101, Australia

Location

Related Publications (27)

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MeSH Terms

Conditions

Ataxia Telangiectasia; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Spinocerebellar Ataxias; Neurocutaneous Syndromes; Genetic Diseases, Inborn; Primary Immunodeficiency Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Ataxia; Cerebellar Ataxia; Telangiectasis

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Movement Disorders; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ectodermal Dysplasia; Abnormalities, Multiple; Congenital Abnormalities; Skin Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• David Coman, MBBS FRACP

  Queensland Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Coman, MBBS FRACP

CONTACT

+610730681111; david.coman@health.qld.gov.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 1. Primary objective: Single arm open-label clinical trial in ataxia-telangiectasia to test the effects of nicotinamide riboside on ataxia scales, immune function, and neurofilament light chain. 2. Secondary objectives: * Determine to what extent the beneficial effects ongoing of NR on NFl translate to clinical efficacy in patients with A-T. * Type 1 Interferon (INFs) epigenetic signature specifically the cGAS-STING pathway.

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: March 22, 2024
• Study Start: May 1, 2024
• Primary Completion: October 30, 2025
• Study Completion: October 30, 2025
• Last Updated: April 18, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)