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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
University Hospital, Akershus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ataxia Telangiectasia focused on measuring ataxia telangiectasia, nicotinamide ribonucleoside, Louis-Bar syndrome

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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
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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.
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NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia

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