Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000781549
Ethics application status
Approved
Date submitted
11/06/2024
Date registered
25/06/2024
Date last updated
25/06/2024
Date data sharing statement initially provided
25/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
STRENGTH Study: Supplement Treatment Evaluation of L-carnitine for Muscle Fatigue and Weakness in Children with Neurofibromatosis Type 1
Scientific title
A Randomized, Double-Blind, Placebo Controlled, Phase 3 Study Assessing the Efficacy and Safety of L-carnitine Supplementation to Treat Muscle Fatigue and Weakness in Children with Neurofibromatosis Type 1
Secondary ID [1] 312313 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record
A follow up study of ACTRN12618002021257

Health condition
Health condition(s) or problem(s) studied:
Neurofibromatosis Type 1 334068 0
Condition category
Condition code
Musculoskeletal 330735 330735 0 0
Other muscular and skeletal disorders
Metabolic and Endocrine 330736 330736 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 330737 330737 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will be prescribed a daily dose of L-carnitine equivalent to the nearest 500 mg dose of 50 mg/kg/day or placebo, given as a split dose to be taken at breakfast and at dinner. L-carnitine can either be given as hard capsules (500 mg) or as a powder for those seeking to avoid taking larger numbers of capsules.

Participants will visit the study centres every 6 weeks during the intervention period for 12 weeks, then have a one-week washout. After Week 12 visit eligible patients will move on to the crossover study. This will be a further 12-week Treatment/Supplementation period.

The purpose of study visits Week 6 and Week 12 is to undertake outcome assessments, complete patient and parent questionnaires and to provide more supplements to patients.

Crossover period is when patients switch over between intervention arm and placebo arm.

To monitor patient's adherence to the intervention a dosing diary will be provided to participants/guardians every study visits along with the IP tablets when they are dispensed. This will include date and time IP was taken by the patient and reasons if they were missed. Also, a robust process of counting leftover IP upon return will be done by the trial pharmacists and nurses and will be recorded on the patients' and pharmacy files.
Intervention code [1] 328788 0
Treatment: Drugs
Comparator / control treatment
Placebo treatment:

A placebo is a microcellulose capsule that will appear as a white, oblong capsule in a HDPE (High Density Polyethylene) bottle with CRC (Child-resistant closure) lid containing 60 capsules with no active ingredient similar to the IP.

The placebo dose will be two capsules daily for 12 weeks given on split doses -- day and night doses. There will be a one week of washout period followed by another 12 weeks with same dose of 2 capsules daily given day and night.

To monitor patient's adherence to the intervention a dosing diary will be provided to participants/guardians every study visits along with the IP tablets when they are dispensed. This will include date and time IP was taken by the patient and reasons if they were missed. Also, a robust process of counting leftover IP upon return will be done by the trial pharmacists and nurses and will be recorded on the patients' and pharmacy files.
Control group
Placebo

Outcomes
Primary outcome [1] 338500 0
Objective clinical evaluation of NF1 patients’ muscular strength through percent change in ankle dorsiflexion and plantarflexion from Baseline to Week 12 and Week 25.

This is a composite primary outcome.
Timepoint [1] 338500 0
Baseline is randomisation and the commencement of intervention
Week 12 and Week 25 will be post-intervention clinical and functional assessments
Primary outcome [2] 338585 0
Objective clinical evaluation of NF1 patients’ muscular strength through percent change in the maximum isometric strength of the hand and forearm muscles as a result of hand-grip strength test from Baseline to Week 12 and Week 25.
Timepoint [2] 338585 0
Baseline is randomisation and the commencement of intervention
Week 12 and Week 25 will be post-intervention clinical and functional assessments
Primary outcome [3] 338586 0
Objective clinical evaluation of NF1 patients’ performance capacity and endurance through percent change of distance covered over a time of 6 minutes from Baseline to Week 12 and Week 25.
Timepoint [3] 338586 0
Baseline is randomisation and the commencement of intervention
Week 12 and Week 25 will be post-intervention clinical and functional assessments
Secondary outcome [1] 436184 0
To determine safety of 50mg/kg/day of L-carnitine in patients aged 8 to 12 years who fulfill the National Institutes of Health Consensus Conference diagnostic criteria for NF1 who have a self-reported history of muscle weakness.
Timepoint [1] 436184 0
Baseline is randomisation and the commencement of intervention
Week 6, Week 12 and Week 25 will be post-intervention clinical examination and functional assessments
Secondary outcome [2] 436185 0
To evaluate treatment effects on physical activity level.
Timepoint [2] 436185 0
Baseline is randomisation and the commencement of intervention
Week 6, Week 12 and Week 25 will be post-intervention clinical examination and functional assessments
Secondary outcome [3] 436504 0
To determine tolerability of 50mg/kg/day of L-carnitine in patients aged 8 to 12 years who fulfill the National Institutes of Health Consensus Conference diagnostic criteria for NF1 who have a self-reported history of muscle weakness.
Timepoint [3] 436504 0
Baseline is randomisation and the commencement of intervention
Week 6, Week 12 and Week 25 will be post-intervention clinical examination and functional assessments

Eligibility
Key inclusion criteria
1. Patients aged 8 to 12 years and 13-17 years of age in the expanded age range, in the event of recruitment difficulty who fulfill the National Institutes of Health Consensus Conference diagnostic criteria for NF1 who have a self-reported history of muscle weakness will be invited to participate and

2. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
Minimum age
8 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Have a severe cognitive impairment.
2. Unable to understand the PICF, and the study including requirements, benefits, and risks even with the assistance of an interpreter or a translator
3. Seizures
4. Skeletal abnormalities, e.g., tibial bowing and pseudarthrosis, acute foot or lower limb injuries, e.g., fracture and ankle sprain
5. Incapacity to comply with a research protocol, e.g., prolonged absence.
6. Have taken carnitine within the last month before commencing the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation through computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using randomisation table created by computer
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The change from baseline in all outcomes (both absolute and percentage change) will be calculated. Spearman’s rank-order correlation efficiency will be applied to determine a weight specific dosage effect.

Based on outcomes from the phase 2a study (ACTRN12618002021257), a power calculation suggests a sample size of 12 vs 12 would be sufficiently powered to show a statistical difference for grip strength, foot dorsiflexion, plantarflexion and six-minute walk test. The study aims to recruit at least 30 patients, with a maximum of 40.

In this study, patients will be randomly assigned to carnitine followed by placebo or placebo followed by carnitine. All patients will have a washout period of one week between treatment and placebo.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
29/07/2024
Actual
Date of last participant enrolment
Anticipated
15/04/2025
Actual
Date of last data collection
Anticipated
15/09/2025
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 26671 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 42711 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 316708 0
Charities/Societies/Foundations
Name [1] 316708 0
Children's Tumor Foundation
Country [1] 316708 0
United States of America
Primary sponsor type
Hospital
Name
Royal North Shore Hospital
Address
Country
Australia
Secondary sponsor category [1] 318987 0
None
Name [1] 318987 0
Address [1] 318987 0
Country [1] 318987 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315485 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 315485 0
Ethics committee country [1] 315485 0
Australia
Date submitted for ethics approval [1] 315485 0
08/01/2024
Approval date [1] 315485 0
28/03/2024
Ethics approval number [1] 315485 0
2024/ETH00028

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 134842 0
A/Prof Yemima Berman
Address 134842 0
Level 3E Acute Services Building, Department of Clinical Genetics, Royal North Shore Hospital, Reserve Road, St Leonards, 2065 NSW
Country 134842 0
Australia
Phone 134842 0
+61 2 9463 1727
Fax 134842 0
Email 134842 0
[email protected]
Contact person for public queries
Name 134843 0
A/Prof Yemima Berman
Address 134843 0
Level 3E Acute Services Building, Department of Clinical Genetics, Royal North Shore Hospital, Reserve Road, St Leonards, 2065 NSW
Country 134843 0
Australia
Phone 134843 0
+61 2 9463 1727
Fax 134843 0
Email 134843 0
[email protected]
Contact person for scientific queries
Name 134844 0
A/Prof Yemima Berman
Address 134844 0
Level 3E Acute Services Building, Department of Clinical Genetics, Royal North Shore Hospital, Reserve Road, St Leonards, 2065 NSW
Country 134844 0
Australia
Phone 134844 0
+61 2 9463 1727
Fax 134844 0
Email 134844 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data underlying published results only, following de-identification.
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
Anyone who wishes to access it
Available for what types of analyses?
The data will be available for any purpose
How or where can data be obtained?
The findings from this clinical trial will be disseminated through academic publications, peer-reviewed journals, and conference presentations.
Individual Participant Data underlying published results may be requested by emailing the principal investigator at [email protected]


What supporting documents are/will be available?




Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.