NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia
Primary Purpose
Ataxia Telangiectasia
Status
Active
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Nicotinamide ribonucleoside
Sponsored by
About this trial
This is an interventional treatment trial for Ataxia Telangiectasia focused on measuring ataxia telangiectasia, nicotinamide ribonucleoside, Louis-Bar syndrome
Eligibility Criteria
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
Sites / Locations
- Hilde Loge Nilsen
- Oslo University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
NR treated
Arm Description
Nicotinamide ribonuceloside (NR), sold under the trade name Niagen™
Outcomes
Primary Outcome Measures
NAD metabolome
Increase of NAD+ and other stable NAD+ metabolites (referred to as the NAD metabolome) in blood
Secondary Outcome Measures
Patient well being
Improved or stabilized health-related quality of life (HRQOL) measured with the Pediatric Quality of Life Inventory (PedSQL)
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).
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).
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).
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).
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).
Liver function
Normalized or stabilized liver function as assessed by blood levels of
-alfa fetoprotein (AFP)
Blood sugar control
Normalized or stabilized blood sugar levels as measured in blood:
-HbA1c
Mitochondrial function
Normalized or stabilized mitochondrial markers in blood:
lactate
lactate dehydrogenase
FGF21
Full Information
NCT ID
NCT04870866
First Posted
April 23, 2021
Last Updated
August 16, 2022
Sponsor
University Hospital, Akershus
Collaborators
The Bergesen Foundation, South-Eastern Norway Regional Health Authority, Sykehuset Innlandet HF, Oslo University Hospital, St. Olavs Hospital, Haukeland University Hospital, University Hospital of North Norway, University of Bergen
1. Study Identification
Unique Protocol Identification Number
NCT04870866
Brief Title
NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia
Official Title
NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 5, 2019 (Actual)
Primary Completion Date
September 3, 2024 (Anticipated)
Study Completion Date
June 16, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Akershus
Collaborators
The Bergesen Foundation, South-Eastern Norway Regional Health Authority, Sykehuset Innlandet HF, Oslo University Hospital, St. Olavs Hospital, Haukeland University Hospital, University Hospital of North Norway, University of Bergen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ataxia Telangiectasia
Keywords
ataxia telangiectasia, nicotinamide ribonucleoside, Louis-Bar syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open label proof of concept
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NR treated
Arm Type
Experimental
Arm Description
Nicotinamide ribonuceloside (NR), sold under the trade name Niagen™
Intervention Type
Drug
Intervention Name(s)
Nicotinamide ribonucleoside
Other Intervention Name(s)
Niagen
Intervention Description
Two year intervention
Primary Outcome Measure Information:
Title
NAD metabolome
Description
Increase of NAD+ and other stable NAD+ metabolites (referred to as the NAD metabolome) in blood
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Patient well being
Description
Improved or stabilized health-related quality of life (HRQOL) measured with the Pediatric Quality of Life Inventory (PedSQL)
Time Frame
2 years
Title
Motoric function - The Scale for the Assessment and Rating of Ataxia (SARA)
Description
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).
Time Frame
2 years
Title
Motoric function - The International Cooperative Ataxia Rating Scale (ICARS)
Description
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).
Time Frame
2 years
Title
Motoric function - Customized gait scale (GS)
Description
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).
Time Frame
2 years
Title
Motoric function - AT Neuro Examination Scale Toolkit, updated version (AT-NEST)
Description
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).
Time Frame
2 years
Title
Motoric function - Clinical Global Scale rating instrument for A-T
Description
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).
Time Frame
2 years
Title
Liver function
Description
Normalized or stabilized liver function as assessed by blood levels of
-alfa fetoprotein (AFP)
Time Frame
2 years
Title
Blood sugar control
Description
Normalized or stabilized blood sugar levels as measured in blood:
-HbA1c
Time Frame
2 years
Title
Mitochondrial function
Description
Normalized or stabilized mitochondrial markers in blood:
lactate
lactate dehydrogenase
FGF21
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hilde L Nilsen
Organizational Affiliation
University Hospital, Akershus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hilde Loge Nilsen
City
Lørenskog
Country
Norway
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
27732836
Citation
Fang EF, Kassahun H, Croteau DL, Scheibye-Knudsen M, Marosi K, Lu H, Shamanna RA, Kalyanasundaram S, Bollineni RC, Wilson MA, Iser WB, Wollman BN, Morevati M, Li J, Kerr JS, Lu Q, Waltz TB, Tian J, Sinclair DA, Mattson MP, Nilsen H, Bohr VA. NAD+ Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. Cell Metab. 2016 Oct 11;24(4):566-581. doi: 10.1016/j.cmet.2016.09.004.
Results Reference
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NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia
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