Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04513002
Registration number
NCT04513002
Ethics application status
Date submitted
26/07/2020
Date registered
14/08/2020
Date last updated
20/07/2023
Titles & IDs
Public title
Ataxia-telangiectasia: Treating Mitochondrial Dysfunction With a Novel Form of Anaplerosis
Query!
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
Query!
Secondary ID [1]
0
0
A-T2020/01
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
A-TC7
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Ataxia Telangiectasia
0
0
Query!
Condition category
Condition code
Neurological
0
0
0
0
Query!
Other neurological disorders
Query!
Neurological
0
0
0
0
Query!
Neurodegenerative diseases
Query!
Human Genetics and Inherited Disorders
0
0
0
0
Query!
Other human genetics and inherited disorders
Query!
Cardiovascular
0
0
0
0
Query!
Diseases of the vasculature and circulation including the lymphatic system
Query!
Intervention/exposure
Study type
Interventional
Query!
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%, 35%, 35%, 35% (no placebo). Group 2: placebo, 10%, 20%, 35%, 35% Group 3: placebo, placebo, 10%, 20%, 35%
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%, 35%, 35%, 35% (no placebo). Group 2: placebo, 10%, 20%, 35%, 35% Group 3: placebo, placebo, 10%, 20%, 35%
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%, 35%, 35%, 35% (no placebo). Group 2: placebo, 10%, 20%, 35%, 35% Group 3: placebo, placebo, 10%, 20%, 35%
Other interventions: Triheptanoin
Triheptanoin is a highly purified, synthetic medium odd-chain triglyceride that is catabolized to heptanoate.
Query!
Intervention code [1]
0
0
Other interventions
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Nasal epithelial cell survival under conditions of glucose deprivation.
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
Day 1, baseline measurement
Query!
Primary outcome [2]
0
0
Nasal epithelial cell survival under conditions of glucose deprivation.
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
Day 60, assessment of effects/changes from Day 1 baseline measurement
Query!
Primary outcome [3]
0
0
Nasal epithelial cell survival under conditions of glucose deprivation.
Query!
Assessment method [3]
0
0
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.
Query!
Timepoint [3]
0
0
Day 120, assessment of effects/changes from Day 60 baseline measurement
Query!
Primary outcome [4]
0
0
Nasal epithelial cell survival under conditions of glucose deprivation.
Query!
Assessment method [4]
0
0
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.
Query!
Timepoint [4]
0
0
Day 180, assessment of effects/changes from Day 120 baseline measurement
Query!
Primary outcome [5]
0
0
Nasal epithelial cell survival under conditions of glucose deprivation.
Query!
Assessment method [5]
0
0
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.
Query!
Timepoint [5]
0
0
Day 240, assessment of effects/changes from Day 180 baseline measurement
Query!
Primary outcome [6]
0
0
Nasal epithelial cell survival under conditions of glucose deprivation.
Query!
Assessment method [6]
0
0
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.
Query!
Timepoint [6]
0
0
Day 300, assessment of effects/changes from Day 240 baseline measurement
Query!
Primary outcome [7]
0
0
Nasal epithelial cell survival under conditions of glucose deprivation.
Query!
Assessment method [7]
0
0
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.
Query!
Timepoint [7]
0
0
Day 360, assessment of effects/changes from Day 300 baseline measurement
Query!
Secondary outcome [1]
0
0
Scales for assessment and rating of ataxia
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
Day 1, Day 120, Day 240, Day 360
Query!
Secondary outcome [2]
0
0
International Cooperative Ataxia Rating Scale
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
Day 1, Day 120, Day 240, Day 360
Query!
Secondary outcome [3]
0
0
Speech Pathology Assessments
Query!
Assessment method [3]
0
0
Speech perception and intelligibility will be defined using a standardised instrument.
Query!
Timepoint [3]
0
0
Day 1, Day 120, Day 240, Day 360
Query!
Secondary outcome [4]
0
0
Ophthalmology assessments
Query!
Assessment method [4]
0
0
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.
Query!
Timepoint [4]
0
0
Day 1, Day 120, Day 240, Day 360
Query!
Secondary outcome [5]
0
0
MRI lung imaging
Query!
Assessment method [5]
0
0
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.
Query!
Timepoint [5]
0
0
Performed at Day 1 and Day 360 in suitable participants
Query!
Secondary outcome [6]
0
0
Spirometry Vital capacity (litres)
Query!
Assessment method [6]
0
0
Lung function will be measured using conventional spirometry in those able to perform the test.
Query!
Timepoint [6]
0
0
Day 1, Day 120, Day 240, Day 360
Query!
Secondary outcome [7]
0
0
Spirometry Forced vital capacity (litres)
Query!
Assessment method [7]
0
0
Lung function will be measured using conventional spirometry in those able to perform the test.
Query!
Timepoint [7]
0
0
Day 1, Day 120, Day 240, Day 360
Query!
Secondary outcome [8]
0
0
Spirometry Forced expiratory volume in one second (litres)
Query!
Assessment method [8]
0
0
Lung function will be measured using conventional spirometry in those able to perform the test.
Query!
Timepoint [8]
0
0
Day 1, Day 120, Day 240, Day 360
Query!
Secondary outcome [9]
0
0
Spirometry Peak expiratory flow (L.min-1)
Query!
Assessment method [9]
0
0
Lung function will be measured using conventional spirometry in those able to perform the test.
Query!
Timepoint [9]
0
0
Day 1, Day 120, Day 240, Day 360
Query!
Secondary outcome [10]
0
0
Upper respiratory microbiome
Query!
Assessment method [10]
0
0
DNA extraction and sequencing via Qiagen DNA isolation kit then 16S rRNA sequencing16S rRNA sequencing
Query!
Timepoint [10]
0
0
Day 1, Day 60, Day 120, Day 180, Day 240, Day 300, Day 360
Query!
Secondary outcome [11]
0
0
Faecal microbiome
Query!
Assessment method [11]
0
0
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.
Query!
Timepoint [11]
0
0
Day 1, Day 60, Day 120, Day 180, Day 240, Day 300, Day 360
Query!
Secondary outcome [12]
0
0
Intestinal permeability
Query!
Assessment method [12]
0
0
Lipopolysaccharide, Lipopolysaccharide binding protein and Zonulin analys by standard ELISA assays.
Query!
Timepoint [12]
0
0
Day 1, Day 60, Day 120, Day 180, Day 240, Day 300, Day 360
Query!
Eligibility
Key inclusion criteria
- 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.
Query!
Minimum age
No limit
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- 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
- Intestinal Malabsorption secondary to Pancreatic Insufficiency
- 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.
Query!
Study design
Purpose of the study
Health Services Research
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
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
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
15/03/2022
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
10/07/2023
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
30
Query!
Recruitment in Australia
Recruitment state(s)
QLD
Query!
Recruitment hospital [1]
0
0
Queensland Children's Hospital - Brisbane
Query!
Recruitment postcode(s) [1]
0
0
4001 - Brisbane
Query!
Funding & Sponsors
Primary sponsor type
Other
Query!
Name
The University of Queensland
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Other
Query!
Name [1]
0
0
National Health and Medical Research Council, Australia
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
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%, 35%, 35%, 35% (no placebo). Group 2:
placebo, 10%, 20%, 35%, 35% Group 3: placebo, placebo, 10%, 20%, 35%.
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 neuroflament light chain.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT04513002
Query!
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.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
David Coman, MBBS FRACP
Query!
Address
0
0
Queensland Children's Hospital
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04513002
Download to PDF