CREAT_criteria: Relevant Outcome Measures for Creatine Transporter Deficiency Patient
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: CTD patients Case group 24 male CTD patients having a confirmed mutation in the SLC6A8 gene, aged > 5 to < 35 years. |
Other: Clinical endpoints
Number of epileptic seizures
Change in antiepileptic treatment (increase or decrease)
Visual analogical scale on a target symptom defined with the parents,
CGI,
Actimetry data over 24 hours,
Podometry data over 24 hours,
6 minutes' walk test,
Clinical examination
Feasibility of performing an MRI without any anesthesia on a mock scanner
Other: Parental questionnaires
10- Adaptive assessment with Vineland Adaptive Behavior scale II,
11- Mac Arthur questionnaire regarding language,
12- Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS),
13- Dunn sensory profile,
14- Aberrant Behavior Checklist,
15- Nisonger Child Behavior Rating form,
16- Social Responsiveness Scale 2,
17- Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)
Other: Quality of life scale
18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)
Other: Cognitive assessments
19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible
20- CPM-BF
21- Simple reasoning task on tablet (match-to-sample task)
22- Implicit rules learning (modified Brixton),
23- 4 sub-tests from the WPPSI-IV ("zoo location" to assess spatial memory, "block design" to assess visuo-constructive abilities, "bug search" , "cancellation"),
24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),
25- Elementary visuo-spatial perception (on tablets)
Other: Language assessments
26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments),
27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary),
28- Automatic language analysis (during a 10 minutes interaction, play).
Other: Motor assessments
29- Kinematic task (specifically designed),
30- Purdue-Pegboard test,
31- Renzi test
Other: Social assessments
32- Eye-tracking analysis of social visual scenes and social preference index (movies),
33- theory of mind assessment,
34- ADOS scale (Autism Spectrum Disorder),
35- sensitivity to inequality,
36- pro-social behaviors (help of the psychologist)
Other: 3T MRI
37- Structural, metabolic and functional data
Other: Cardiac assessments
38- ECG
39- Ultrasound
Other: Biological collection
40- Blood sample
41- Urinary sample
42- Superficial skin biopsy
|
| Other: Sex and chronological age matched controls Control group 24 male, sex and chronological age matched controls, aged > 5 to < 35 years |
Other: Clinical endpoints
Number of epileptic seizures
Change in antiepileptic treatment (increase or decrease)
Visual analogical scale on a target symptom defined with the parents,
CGI,
Actimetry data over 24 hours,
Podometry data over 24 hours,
6 minutes' walk test,
Clinical examination
Feasibility of performing an MRI without any anesthesia on a mock scanner
Other: Quality of life scale
18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)
Other: Cognitive assessments
19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible
20- CPM-BF
21- Simple reasoning task on tablet (match-to-sample task)
22- Implicit rules learning (modified Brixton),
23- 4 sub-tests from the WPPSI-IV ("zoo location" to assess spatial memory, "block design" to assess visuo-constructive abilities, "bug search" , "cancellation"),
24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),
25- Elementary visuo-spatial perception (on tablets)
Other: Language assessments
26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments),
27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary),
28- Automatic language analysis (during a 10 minutes interaction, play).
Other: Motor assessments
29- Kinematic task (specifically designed),
30- Purdue-Pegboard test,
31- Renzi test
Other: Social assessments
32- Eye-tracking analysis of social visual scenes and social preference index (movies),
33- theory of mind assessment,
34- ADOS scale (Autism Spectrum Disorder),
35- sensitivity to inequality,
36- pro-social behaviors (help of the psychologist)
Other: 3T MRI
37- Structural, metabolic and functional data
|
| Other: Sex and mental age matched controls Control group 24 male, sex and mental age matched controls, aged > 3 to < 8 years |
Other: Parental questionnaires
10- Adaptive assessment with Vineland Adaptive Behavior scale II,
11- Mac Arthur questionnaire regarding language,
12- Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS),
13- Dunn sensory profile,
14- Aberrant Behavior Checklist,
15- Nisonger Child Behavior Rating form,
16- Social Responsiveness Scale 2,
17- Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)
Other: Quality of life scale
18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)
Other: Cognitive assessments
19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible
20- CPM-BF
21- Simple reasoning task on tablet (match-to-sample task)
22- Implicit rules learning (modified Brixton),
23- 4 sub-tests from the WPPSI-IV ("zoo location" to assess spatial memory, "block design" to assess visuo-constructive abilities, "bug search" , "cancellation"),
24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),
25- Elementary visuo-spatial perception (on tablets)
Other: Language assessments
26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments),
27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary),
28- Automatic language analysis (during a 10 minutes interaction, play).
Other: Motor assessments
29- Kinematic task (specifically designed),
30- Purdue-Pegboard test,
31- Renzi test
Other: Social assessments
32- Eye-tracking analysis of social visual scenes and social preference index (movies),
33- theory of mind assessment,
34- ADOS scale (Autism Spectrum Disorder),
35- sensitivity to inequality,
36- pro-social behaviors (help of the psychologist)
|
| Other: Typically developed children Control group 80 typically developed children aged > 3 to < 8 years, which corresponds to the mental age of CTD patients. 40 children aged > 3 to < 5 years, and 40 children aged > 6 to < 8 years will perform the newly developed outcome measures. |
Other: Parental questionnaires
10- Adaptive assessment with Vineland Adaptive Behavior scale II,
11- Mac Arthur questionnaire regarding language,
12- Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS),
13- Dunn sensory profile,
14- Aberrant Behavior Checklist,
15- Nisonger Child Behavior Rating form,
16- Social Responsiveness Scale 2,
17- Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)
Other: Quality of life scale
18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)
Other: Cognitive assessments
19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible
20- CPM-BF
21- Simple reasoning task on tablet (match-to-sample task)
22- Implicit rules learning (modified Brixton),
23- 4 sub-tests from the WPPSI-IV ("zoo location" to assess spatial memory, "block design" to assess visuo-constructive abilities, "bug search" , "cancellation"),
24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),
25- Elementary visuo-spatial perception (on tablets)
Other: Language assessments
26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments),
27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary),
28- Automatic language analysis (during a 10 minutes interaction, play).
Other: Motor assessments
29- Kinematic task (specifically designed),
30- Purdue-Pegboard test,
31- Renzi test
Other: Social assessments
32- Eye-tracking analysis of social visual scenes and social preference index (movies),
33- theory of mind assessment,
34- ADOS scale (Autism Spectrum Disorder),
35- sensitivity to inequality,
36- pro-social behaviors (help of the psychologist)
|
Outcome Measures
Primary Outcome Measures
- Clinical endpoints : number of epileptic seizures [Up to 90 Days]
Number of epileptic seizures
- Clinical endpoints : antiepileptic treatment [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).]
Change in antiepileptic treatment (increase or decrease)
- Clinical endpoints : Visual analogical scale [Up to 90 Days]
Visual analogical scale on a target symptom defined with the parents,
- Clinical endpoints : actimetry [Up to 90 Days]
Actimetry data over 48 hours
- Clinical endpoints : podometry [Up to 90 Days]
Podometry data over 24 hours
- Clinical endpoints : walk test [Up to 90 Days]
6 minutes' walk test
- Clinical endpoints : Clinical examination [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 examination
- Clinical endpoints :Feasibility of performing an MRI [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).]
Feasibility of performing an MRI without any anesthesia on a mock scanner
- Parental questionnaires : Vineland Adaptive Behavior scale II [For all 24 CTD patients: V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).]
Adaptive assessment with Vineland Adaptive Behavior scale II
- Parental questionnaires : Mac Arthur questionnaire [For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).]
Mac Arthur questionnaire regarding language
- Parental questionnaires : PDD-MRS [For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).]
Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS)
- Parental questionnaires : Dunn sensory profile [For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).]
Dunn sensory profile
- Parental questionnaires : Aberrant Behavior Checklist [For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).]
Aberrant Behavior Checklist
- Parental questionnaires : Nisonger Child Behavior Rating form [For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).]
Nisonger Child Behavior Rating form
- Parental questionnaires : Social Responsiveness Scale 2 [For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).]
Social Responsiveness Scale 2
- Parental questionnaires : impact on primary caregiver [For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).]
Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)
- Quality of life scale [For all 24 CTD patients: At V1 (Day1/Day2) For 9 out of 24 CTD patients: Repeated at V3 (Day30) and V7 (Day90).]
Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)
- Cognitive assessments : Leiter 3 scale [For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1)]
Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible
- Cognitive assessments : CPM-BF [For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1)]
CPM-BF : Raven's coloured Progressive Matrices
- Cognitive assessments : reasoning task [For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)]
Simple reasoning task on tablet (match-to-sample task)
- Cognitive assessments : Implicit rules learning [For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)]
Implicit rules learning (modified Brixton),
- Cognitive assessments : WPPSI-IV [For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)]
4 sub-tests from the WPPSI-IV ("zoo location" to assess spatial memory, "block design" to assess visuo-constructive abilities, "bug search" , "cancellation"),
- Cognitive assessments : Attention assessment [For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)]
Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),
- Cognitive assessments : Elementary visuo-spatial perception [For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)]
Elementary visuo-spatial perception (on tablets)
- Language assessments : EXALANG 3-6 [For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)]
EXALANG 3-6 - Computerized battery for the evaluation of oral and written language : 10 sub-tests testing for expressive and receptive language assessments
- Language assessments : vocabulary [For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)]
PPVT-5 : Peabody Picture Vocabulary Test Fifth Edition = receptive vocabulary, EVT-3 : Expressive Vocabulary Test third edition,
- Language assessments : Automatic language analysis [For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)]
Automatic language analysis (during a 10 minutes interaction, play).
- Motor assessments : Kinematic task [CTD patients : performed at V1 (Day1/Day2). Controls: Motor assessment at V1 (Day 1)]
Kinematic task (specifically designed)
- Motor assessments : Purdue-Pegboard test [CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1)]
Purdue-Pegboard test
- Motor assessments : Renzi test [CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1)]
Renzi test
- Social assessments : Eye-tracking [CTD patients : performed at V1 (Day1/Day2), V3 (Day30) and V7 (Day90). Controls : Social assessment at V1(Day1)]
Eye-tracking analysis of social visual scenes and social preference index (movies)
- Social assessments : Theory of mind assessment [CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)]
Theory of mind assessment
- Social assessments : ADOS scale (Autism Diagnostic Observation Scale) [CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)]
ADOS scale (Autism Spectrum Disorder)
- Social assessments : Sensitivity to inequality [CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)]
Sensitivity to inequality
- Social assessments : Pro-social behaviors (help of the psychologist) [CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)]
Pro-social behaviors (help of the psychologist)
Secondary Outcome Measures
- Neuroimaging (MRI) [V1 (Day1/Day2)]
The MRI will be performed to describe structural and functional neuroanatomical profile of CTD patient in comparison to chronological age-matched controls and variability in creatine peak assessment using MR spectroscopy
- Cardiac assessments : Electrocardiogram [CTD patients: V1 (Day1/Day2)]
Electrocardiogram (ECG) will be performed to describe CTD patients cardiac profile (especially the risk of increased QTC and/or cardiac echography abnormality)
- Cardiac assessments : Ultrasound [CTD patients: V1 (Day1/Day2)]
Cardiac Ultrasound will be performed to describe CTD patients cardiac profile (especially the risk of increased QTC and/or cardiac echography abnormality)
- Biological collection : Blood sample [CTD patients: V1 (Day1/Day2)]
Blood sample (plasma and peripheral blood mononuclear cells)
- Biological collection : Urine sample [CTD patients: V1 (Day1/Day2)]
Urine sample will be collected to create a collection of biological samples associated with clinical and genomic data from CTD patients. In the future this will be usefull for research labs to investigate new biomarkers (not identified yet) or to test for the efficiency of new therapeutic approaches in vitro (on cultivated fibroblasts or after the development of iPS cells or organoïds) in this rare disease.
- Biological collection : Superficial skin biopsy [CTD patients: V1 (Day1/Day2)]
Superficial skin biopsy will be performed to get cultivated fibroblasts to create a collection of biological samples associated with clinical and genomic data from CTD patients. In the future this will be usefull for research labs to investigate new biomarkers (not identified yet) or to test for the efficiency of new therapeutic approaches in vitro (on cultivated fibroblasts or after the development of iPS cells or organoïds) in this rare disease.
Eligibility Criteria
Criteria
Inclusion Criteria:
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.
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 mental age-matched controls (n=24)
-
Male
-
Aged > 3 to < 8 years
-
Whose maternal language is French,
-
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.
Typically developed children (n=80)
-
Male and female
-
Aged > 3 to < 8 years
-
Whose maternal language is French,
-
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.
Exclusion Criteria:
CTD patients (n=24):
-
Having a contraindication to the MRI examination (people using a pacemaker or an insulin pump, people wearing a metal prosthesis or an intracerebral clip, and claustrophobic subjects),
-
Refusal of the subject and/or the subject's parents to be informed of possible abnormalities detected by MRI,
-
Refusal of the subject and/or the subject's parents/legal guardian to be informed of possible abnormalities detected during the cardiac assessment.
Sex- and chronological age-matched controls (n=24)
-
History of neurological or psychiatric disorder,
-
Repetition of a grade,
-
Learning disability requiring rehabilitation (speech therapy, psychomotor or oculomotor therapy),
-
For participants agreeing on performing the MRI examination, having a contraindication to the MRI examination (use of a pacemaker or an insulin pump, people wearing a metal prosthesis or an intracerebral clip, and claustrophobic subjects) and refusal of the subject and/or the subject's parents/legal guardian to be informed of possible abnormalities detected by MRI.
Sex- and mental age-matched controls (n=24)
-
History of neurological or psychiatric disorder,
-
Repetition of a grade,
-
Learning disability requiring rehabilitation (speech therapy, psychomotor or oculomotor therapy).
Typically developed children (n=80)
-
History of neurological or psychiatric disorder,
-
Repetition of a grade,
-
Learning disability requiring rehabilitation (speech therapy, psychomotor or oculomotor therapy).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Woman, mother and child hospital, Hospices Civils de Lyon | Bron | France | 69500 |
Sponsors and Collaborators
- Hospices Civils de Lyon
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 69HCL21_0655
- 2022-A02063-40