RecruitingNot Applicable

Relevant Outcome Measures for Creatine Transporter Deficiency Patient

France197 participantsStarted 2023-03-13

Plain-language summary

Creatine transport deficiency (CTD) is a rare genetic disorder related to pathogenic variants in the SLC6A8 gene, located on chromosome Xq28. Clinical diagnosis of CTD is based on clinical presentation, an increased urinary creatine/creatinine ratio and a severe decreased creatine peak on 1H-MRS magnetic resonance spectroscopy. A retrospective study with questionnaires identified that most CTD patients had moderate to severe intellectual disability. Less than one third of patients were able to speak in sentences. Seizures were present in 59% of the patients. 41% had autistic features. Motor dysfunction was mentioned in 58%, and gastrointestinal symptoms were reported in 35% of the patients. Several new therapeutic avenues are currently emerging in this disease for which no treatment has been available until now : cyclocreatine (interesting but unfortunately with very little clinical applicability due to its toxicity; dodecyl creatine ester incorporated into lipid nanocapsules with intranasal administration; pharmaco-chaperoning (for the folding-deficient creatine transporter variants, Ultragenyx pharmaceuticals new prodrug designed to deliver creatine to the brain (UX068). These new pharmacological treatment options may offer future opportunities to improve cognition in CTD patients. A key issue is to determine outcome measures that are accessible to these patients, despite the importance of their cognitive deficit. In a preliminary study (on 31 CTD patients), investigators showed for example, that 75% of patients were unable to perform a Wechsler scale, which is one of the most used neuropsychological test to determine patient IQ (intelligence quotient). Most of the existing cognitive tests were developed to distinguish typically developing persons and ID (intellectual disability) patients, leading to a floor effect in the latter who systematically fail these tests. Therefore, these tests are not adapted to capture the potential effect of a drug in ID patient group. The identification of reliable and sensitive outcome measures for use in clinical trials in ID patients was recognized as a priority in a meeting convened by the NIH. N-of-1 trials (also called Single-Case Experimental Designs or SCEDs) appear of great interest for rare diseases, statistical power coming from the number of repeated measures, which leads to choose outcome measures that can be repeated multiple times. This innovative study will allow to efficiently preparing future therapeutic trials, by specifying the phenotype of the patients, and by determining the most adapted outcome measures taking into account their cognitive deficiency and the type of experimental design to be used in the context of rare diseases.

Who can participate

Age range

2 Years – 60 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: Male CTD patients (n=24) * Male CTD patients having a confirmed mutation in the SLC6A8 gene, * Aged \> 5 to \< 35 years * Whose maternal language is French, * Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent, * Affiliated to national Health Insurance system or parents/legal guardian affiliated to national health insurance system. Female CTD patients (n=15) * Female CTD patients having a confirmed mutation in the SLC6A8 gene, * Aged \> 5 to \< 60 years, * Whose maternal language is French, * Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent. * Affiliated to national Health Insurance system (sécurité sociale) or parents/legal guardian affiliated to national health insurance system Sex- and chronological age-matched controls (n=24) * Male * Aged \> 5 to \< 35 years * Whose maternal language is French, * Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent, * Affiliated to national health insurance system or parents/legal guardian affiliated to national health insurance system. Sex- and chronological age-matched female controls (n=15) * female, * Aged \> 5 to \< 60 years, * Whose maternal language is French, * Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent * Affiliated to national Health Insurance system (sécurité sociale) or p…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Clinical endpoints : number of epileptic seizures

Timeframe: Up to 90 Days

Clinical endpoints : antiepileptic treatment

Timeframe: For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).

Clinical endpoints : Visual analogical scale

Timeframe: Up to 90 Days

Clinical endpoints : actimetry

Timeframe: Up to 90 Days

Clinical endpoints : podometry

Timeframe: Up to 90 Days

Clinical endpoints : walk test

Timeframe: Up to 90 Days

Clinical endpoints : Clinical examination

Trial details

NCT IDNCT06018519

SponsorHospices Civils de Lyon

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2028-12-13

Contact for this trial

Aurore CURIE, MD,PhD

06 70 62 69 76 aurore.curie@chu-lyon.fr

View on ClinicalTrials.gov More Creatine Transporter Defect trials

Plain-language summary

Who can participate

Age range

2 Years – 60 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

Clinical endpoints : number of epileptic seizures

Timeframe: Up to 90 Days

Clinical endpoints : antiepileptic treatment

Clinical endpoints : Visual analogical scale

Timeframe: Up to 90 Days

Clinical endpoints : actimetry

Timeframe: Up to 90 Days

Clinical endpoints : podometry

Timeframe: Up to 90 Days

Clinical endpoints : walk test

Timeframe: Up to 90 Days

Clinical endpoints : Clinical examination