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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04513002




Registration number
NCT04513002
Ethics application status
Date submitted
26/07/2020
Date registered
14/08/2020
Date last updated
14/08/2020

Titles & IDs
Public title
Ataxia-telangiectasia: Treating Mitochondrial Dysfunction With a Novel Form of Anaplerosis
Scientific title
A Phase 2A/2B Placebo-controlled Randomised Clinical Trial to Test the Ability of Triheptanoin to Protect Primary Airway Epithelial Cells Obtained From Participants With Ataxia-telangiectasia Against Death Induced by Glucose Deprivation
Secondary ID [1] 0 0
A-T2020/01
Universal Trial Number (UTN)
Trial acronym
A-TC7
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ataxia Telangiectasia 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Triheptanoin

Other: Group 1: Triheptanoin and no Placebo - Parallel group, placebo-controlled, dose-escalation each 2 months for 12 months. Dose based on percent (%) of calculated caloric intake.
Thirty participants will be randomised in blocks on a 1:1:1 ratio into one of three groups.
Group 1: 10%, 20%, 30%, 30%, 30% (no placebo). Group 2: placebo, 10%, 20%, 30%, 30% Group 3: placebo, placebo, 10%, 20%, 30%

Other: Group 2: Placebo and Triheptanoin - Parallel group, placebo-controlled, dose-escalation each 2 months for 12 months. Dose based on percent (%) of calculated caloric intake.
Thirty participants will be randomised in blocks on a 1:1:1 ratio into one of three groups.
Group 1: 10%, 20%, 30%, 30%, 30% (no placebo). Group 2: placebo, 10%, 20%, 30%, 30% Group 3: placebo, placebo, 10%, 20%, 30%

Other: Group 3: Placebo, Placebo and Triheptanoin - Parallel group, placebo-controlled, dose-escalation each 2 months for 12 months. Dose based on percent (%) of calculated caloric intake.
Thirty participants will be randomised in blocks on a 1:1:1 ratio into one of three groups.
Group 1: 10%, 20%, 30%, 30%, 30% (no placebo). Group 2: placebo, 10%, 20%, 30%, 30% Group 3: placebo, placebo, 10%, 20%, 30%


Other interventions: Triheptanoin
Triheptanoin is a highly purified, synthetic medium odd-chain triglyceride that is catabolized to heptanoate.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Nasal epithelial cell survival under conditions of glucose deprivation. - Submerged epithelial cultures will be established at each visit to the clinic and assays described above carried out within 2 weeks to determine effects of triheptanoin treatment on cell death, mitochondrial function and signalling. The primary outcome variable will be percent cell death induced by glucose deprivation in cell culture.
Timepoint [1] 0 0
14 months
Secondary outcome [1] 0 0
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, escilating numbers in the scale domains indicate increased difficlulty with the measured tasks.
Timepoint [1] 0 0
14 months
Secondary outcome [2] 0 0
International Cooperative Ataxia Rating Scale - International Cooperative Ataxia Rating Scale is a scale recorded out of 100 with 19 items and 4 subscales and has been used in A-T. 0 indicates normal function, escilating numbers in the scale domains indicate increased difficlulty with the measured tasks.
Timepoint [2] 0 0
14 months
Secondary outcome [3] 0 0
Ataxia Telangiectasia Neurological Examination Scale Toolkit - Ataxia Telangiectasia Neurological Examination Scale Toolkit is a scoring system designed to capture the specific features associated with A-T, is is a scale recorded out of 46 with where 0 indicates normal function, escilating numbers in the scale domains indicate increased difficlulty with the measured tasks.
Timepoint [3] 0 0
14 months
Secondary outcome [4] 0 0
Speech Pathology Assessments - Speech perception and intelligibility will be defined using a standardised instrument.
Timepoint [4] 0 0
14 months
Secondary outcome [5] 0 0
Ophthalmology assessments - The EyeSeeCam system will acquire calibrated recordings and quantified analysis of eye movements for assessment of saccadic latency, fixation stability, optokinetic nystagmus and vestibulo-ocular reflex response, and ocular coherence tomography scans provide detailed images of retinal nerve fibre layer.
Timepoint [5] 0 0
14 months
Secondary outcome [6] 0 0
MRI lung imaging - MRI with ultra-short echo time sequences including Pointwise Encoding Time Reduction with Radial Acquisition and Volumetric Interpolated Breath-hold Examination will define lung structure, and diffusion weighted imaging to estimate inflammatory lung changes.
Timepoint [6] 0 0
14 months
Secondary outcome [7] 0 0
Spirometry Vital capacity (litres) - Lung function will be measured using conventional spirometry in those able to perform the test.
Timepoint [7] 0 0
14 months
Secondary outcome [8] 0 0
Spirometry Forced vital capacity (litres) - Lung function will be measured using conventional spirometry in those able to perform the test.
Timepoint [8] 0 0
14 months
Secondary outcome [9] 0 0
Spirometry Forced expiratory volume in one second (litres) - Lung function will be measured using conventional spirometry in those able to perform the test.
Timepoint [9] 0 0
14 months
Secondary outcome [10] 0 0
Spirometry Peak expiratory flow (L.min-1) - Lung function will be measured using conventional spirometry in those able to perform the test.
Timepoint [10] 0 0
14 months
Secondary outcome [11] 0 0
Upper respiratory microbiome - DNA extraction and sequencing via Qiagen DNA isolation kit then 16S rRNA sequencing16S rRNA sequencing
Timepoint [11] 0 0
14 months
Secondary outcome [12] 0 0
Faecal microbiome - DNA extraction and sequencing via Qiagen DNA isolation kit then 16S rRNA sequencing16S rRNA sequencing to identify faecal microbial composition. 1D 1H NMR spectroscopy and gas chromatography for short chain fatty acids and other metabolites.
Timepoint [12] 0 0
14 months
Secondary outcome [13] 0 0
Intestinal permeability - Lipopolysaccharide, Lipopolysaccharide binding protein and Zonulin analys by standard ELISA assays.
Timepoint [13] 0 0
14 months

Eligibility
Key inclusion criteria
- Participants of either sex with a confirmed diagnosis of A-T

- Participants who are able to undertake the study procedures

- Participants who are able to comply with the protocol for its duration and who provide
informed consent signed and dated by parent/legal guardian or adult participant
according to local regulations.
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participants whose parents/legal guardians are not able to provide consent

- Participants who have been in another randomized clinical intervention trial in the
previous 3 months.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Queensland Children's Hospital - Brisbane
Recruitment postcode(s) [1] 0 0
4001 - Brisbane

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Queensland
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Study design: Parallel group, placebo-controlled, dose-escalation each 2 months for 12
months. Dose based on percent (%) of calculated caloric intake. Thirty participants will be
randomised in blocks on a 1:1:1 ratio into one of three groups stratified by age (< 5 years,
5-10 years, > 10 years of age). Group 1: 10%, 20%, 30%, 30%, 30% (no placebo). Group 2:
placebo, 10%, 20%, 30%, 30% Group 3: placebo, placebo, 10%, 20%, 30%.

Primary endpoint: The percent cell death induced by glucose deprivation in cell culture.
Secondary endpoints include: Scales for assessment and rating of ataxia, International
Cooperative Ataxia Rating Scale, Ataxia Telangiectasia Neurological Examination Scale
Toolkit, speech and language assessment, EyeSeeCam assessment, MRI lung imaging, Lung
function, Upper respiratory microbiome, Faecal microbiome, Survival and inflammatory
phenotype of airway epithelial cells, macrophages and in serum, Metabolomic biomarker
discovery in serum and measurement of neuroflamen light chain.
Trial website
https://clinicaltrials.gov/show/NCT04513002
Trial related presentations / publications
Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT. ATM activation by oxidative stress. Science. 2010 Oct 22;330(6003):517-21. doi: 10.1126/science.1192912.
Public notes

Contacts
Principal investigator
Name 0 0
David Coman, MBBS FRACP
Address 0 0
Queensland Children's Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
David Coman, MBBS FRACP
Address 0 0
Country 0 0
Phone 0 0
+61730681111
Fax 0 0
Email 0 0
david.coman@health.qld.gov.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04513002