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Evaluation of Membrane Phospholipid and Energy Metabolism in Subjects at High Risk of Psychotic Transition (MR7T-UHR)

Primary Purpose

Patients With Ultra High Risk of Psychotic Transition

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Cerebral MRI with Phosphorus 31 Magnetic Resonance Spectroscopy
Sponsored by
Centre Hospitalier Henri Laborit
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Patients With Ultra High Risk of Psychotic Transition

Eligibility Criteria

15 Years - 25 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for the UHR group: Patient between 15 and 25 years old Patient fulfilling the UHR criteria objectified by the Comprehensive Assessment of At Risk Mental State scale (CAARMS) and by the social and professional functioning assessment scale (SOFAS) (the "Vulnerability" group is also taken into account, combining first-degree history and functional impact.) Patient with no contraindication to performing a 7T MRI examination Affiliated patient or beneficiary of a social security scheme. Free, informed consent, written and signed by the participant, the investigator and the legal representative if applicable (at the latest on the day of inclusion and before any examination required by the research). Inclusion Criteria for the Control group: Subjects aged 15 to 25 years old, healthy volunteer subject or subject to benefit from an imaging examination, not presenting the criteria of a mental health disorder objectified by a medical interview Subject with no contraindication to performing a 7T MRI examination Affiliated subject or beneficiary of a social security scheme. Free, informed and written consent signed by the participant, the investigator and the legal representative if applicable (at the latest on the day of inclusion and before any examination required by the research). Exclusion Criteria for the UHR group: Patient not at risk or already in a psychotic pathological process according to DSM-5 criteria. Patient already receiving antipsychotic treatment or whose background treatment was changed less than a month ago. Patient presenting an absolute contraindication to 7T MRI such as: foreign bodies (intracranial clips, vascular magnetic clips, cardiac or neural pacemakers, stents, coils, implantable chamber, intracorporeal metallic splinters, cochlear implants, intracorporeal metallic foreign bodies, mechanical heart valve, implanted injection pump, non-removable piercings), pregnant woman, allergy to contrast products, moderate to severe renal insufficiency, breastfeeding, implanted contraception, tinnitus, claustrophobia and braces. The relative contraindications are to be considered, namely: previous surgical interventions, medically implanted device, tattoo or permanent make-up. Exclusion criteria for the control group: - Subject presenting an absolute contraindication to 7T MRI such as: foreign bodies (intracranial clips, vascular magnetic clips, cardiac or neural pacemakers, stents, coils, implantable chamber, intracorporeal metallic fragments, cochlear implants, intracorporeal metallic foreign bodies, valve mechanical heart, implanted injection pump, non-removable piercings), pregnant woman, allergy to contrast products, moderate to severe renal insufficiency, breast-feeding, implanted contraception, tinnitus, claustrophobia and braces. The relative contraindications are to be considered, namely: previous surgical interventions, medically implanted device, tattoo or permanent make-up.

Sites / Locations

  • Centre Hospitalier Henri LaboritRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Patient group

Control group

Arm Description

Participants of this group are subjects with ultra high risk of psychotic transition. At inclusion visit, subjects will have a psychiatric evaluation and a cerebral MRI examination with phosphorus 31 Magnetic Resonance Spectroscopy in order to investigate membrane phospholipid metabolism and cellular energy metabolism. One and two years after the inclusion visit, subjects will have a psychiatric evaluation in order to objectivize if a psychotic transition has occured.

Participants of this group are healthy volunteers. Subjects will have one single visit with a psychiatric evaluation and a cerebral MRI examination with phosphorus 31 Magnetic Resonance Spectroscopy in order to investigate membrane phospholipid metabolism and cellular energy metabolism.

Outcomes

Primary Outcome Measures

Difference of cellular inorganic phosphate between UHR-T and UHR-NT patients.
Levels measurements of inorganic phosphate.
Difference of cellular phosphocreatine between UHR-T and UHR-NT patients.
Levels measurements of phosphocreatine.
Difference of cellular Gamma ATP between UHR-T and UHR-NT patients.
Levels measurements of Gamma ATP.
Difference of cellular Alpha ATP between UHR-T and UHR-NT patients.
Levels measurements of Alpha ATP.
Difference of cellular beta ATP between UHR-T and UHR-NT patients.
Levels measurements of beta ATP.
Difference of intracellular pH between UHR-T and UHR-NT patients.
Levels measurements of intracellular pH.
Difference of membrane phosphodiester alterations between UHR-T and UHR-NT patients.
Levels measurements of phosphodiester.
Difference of membrane phosphomonoester alterations between UHR-T and UHR-NT patients.
Levels measurements of phosphomonoester.

Secondary Outcome Measures

Difference of cellular inorganic phosphate between UHR subjects and control subjects.
Levels measurements of inorganic phosphate.
Difference of cellular phosphocreatine between UHR subjects and control subjects.
Levels measurements of phosphocreatine.
Difference of cellular Gamma ATP between UHR subjects and control subjects.
Levels measurements of Gamma ATP.
Difference of cellular Alpha ATP between UHR subjects and control subjects.
Levels measurements of Alpha ATP.
Difference of cellular beta ATP between UHR subjects and control subjects.
Levels measurements of beta ATP.
Difference of cellular intracellular pH between UHR subjects and control subjects.
Levels measurements of intracellular pH.
Difference of membrane phosphodiester alterations between UHR subjects and control subjects.
Levels measurements of phosphodiester.
Difference of membrane phosphomonoester alterations between UHR subjects and control subjects.
Levels measurements of phosphomonoester.

Full Information

First Posted
April 21, 2022
Last Updated
August 18, 2023
Sponsor
Centre Hospitalier Henri Laborit
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1. Study Identification

Unique Protocol Identification Number
NCT05865652
Brief Title
Evaluation of Membrane Phospholipid and Energy Metabolism in Subjects at High Risk of Psychotic Transition
Acronym
MR7T-UHR
Official Title
Evaluation of Membrane Phospholipid Metabolism and Cellular Energy Metabolism in Subjects at High Risk of Psychotic Transition
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 2, 2023 (Actual)
Primary Completion Date
May 2025 (Anticipated)
Study Completion Date
May 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Henri Laborit

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The management of schizophrenia is a major public health issue, due to its particularly disabling psychotic symptoms and their onset at an early age, typically in adolescents or young adults. The physiopathological hypothesis of an anomaly relating to the renewal of cell membranes and energy metabolism in schizophrenia was proposed as early as the 1930s. This is based on anomalies at certain times in the development of the balance between phosphomonesters, precursors of membrane phospholipids, and phosphodiesters, catabolites of membrane phospholipids. Alterations of these different balances sign neurodevelopmental disorders, and can be objectified by specific techniques such as phosphorus-31 magnetic resonance spectroscopy (SMR-31P). This is used in particular to characterize the energy metabolism of the brain and allows in vivo quantification of phosphorus metabolites. The application of SMR-31P techniques to assess the metabolism of membrane phospholipids and cellular energy metabolism in subjects at high risk of psychotic transition could make it possible to objectify a difference between subjects subsequently suffering from a psychotic transition compared to those who do not suffer from it. Alterations in the metabolism of membrane phospholipids could thus represent a biomarker of psychotic transition. Secondarily, this approach would make it possible to provide elements as to the validity as a diagnosis of this category, which is very heterogeneous in its future. Among the Ultra High Risk (UHR) group, subjects with a psychotic transition (UHR-T) are compared to subjects without this transition (UHR-NT) during the two years of follow-up. The UHR group is compared to the control group. At T0, UHR patients and healthy volunteers will perform brain MRI with Phosphorus 31 magnetic resonance spectroscopy. UHR patients will then be reviewed: at T+1 year for a clinical assessment medical interview to assess the patient's functioning and the appearance of symptoms; at T+2 years for the realization of a follow-up interview with passing of the scales CAARMS (Comprehensive Assessment of At Risk Mental State) and SOFAS (scale of evaluation of the social and professional functioning) in order to determine if the subject belongs to the UHR-T or UHR-NT group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patients With Ultra High Risk of Psychotic Transition

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patient group
Arm Type
Experimental
Arm Description
Participants of this group are subjects with ultra high risk of psychotic transition. At inclusion visit, subjects will have a psychiatric evaluation and a cerebral MRI examination with phosphorus 31 Magnetic Resonance Spectroscopy in order to investigate membrane phospholipid metabolism and cellular energy metabolism. One and two years after the inclusion visit, subjects will have a psychiatric evaluation in order to objectivize if a psychotic transition has occured.
Arm Title
Control group
Arm Type
Active Comparator
Arm Description
Participants of this group are healthy volunteers. Subjects will have one single visit with a psychiatric evaluation and a cerebral MRI examination with phosphorus 31 Magnetic Resonance Spectroscopy in order to investigate membrane phospholipid metabolism and cellular energy metabolism.
Intervention Type
Diagnostic Test
Intervention Name(s)
Cerebral MRI with Phosphorus 31 Magnetic Resonance Spectroscopy
Intervention Description
Cerebral MRI with Phosphorus 31 Magnetic Resonance Spectroscopy
Primary Outcome Measure Information:
Title
Difference of cellular inorganic phosphate between UHR-T and UHR-NT patients.
Description
Levels measurements of inorganic phosphate.
Time Frame
2 years
Title
Difference of cellular phosphocreatine between UHR-T and UHR-NT patients.
Description
Levels measurements of phosphocreatine.
Time Frame
2 years
Title
Difference of cellular Gamma ATP between UHR-T and UHR-NT patients.
Description
Levels measurements of Gamma ATP.
Time Frame
2 years
Title
Difference of cellular Alpha ATP between UHR-T and UHR-NT patients.
Description
Levels measurements of Alpha ATP.
Time Frame
2 years
Title
Difference of cellular beta ATP between UHR-T and UHR-NT patients.
Description
Levels measurements of beta ATP.
Time Frame
2 years
Title
Difference of intracellular pH between UHR-T and UHR-NT patients.
Description
Levels measurements of intracellular pH.
Time Frame
2 years
Title
Difference of membrane phosphodiester alterations between UHR-T and UHR-NT patients.
Description
Levels measurements of phosphodiester.
Time Frame
2 years
Title
Difference of membrane phosphomonoester alterations between UHR-T and UHR-NT patients.
Description
Levels measurements of phosphomonoester.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Difference of cellular inorganic phosphate between UHR subjects and control subjects.
Description
Levels measurements of inorganic phosphate.
Time Frame
2 years
Title
Difference of cellular phosphocreatine between UHR subjects and control subjects.
Description
Levels measurements of phosphocreatine.
Time Frame
2 years
Title
Difference of cellular Gamma ATP between UHR subjects and control subjects.
Description
Levels measurements of Gamma ATP.
Time Frame
2 years
Title
Difference of cellular Alpha ATP between UHR subjects and control subjects.
Description
Levels measurements of Alpha ATP.
Time Frame
2 years
Title
Difference of cellular beta ATP between UHR subjects and control subjects.
Description
Levels measurements of beta ATP.
Time Frame
2 years
Title
Difference of cellular intracellular pH between UHR subjects and control subjects.
Description
Levels measurements of intracellular pH.
Time Frame
2 years
Title
Difference of membrane phosphodiester alterations between UHR subjects and control subjects.
Description
Levels measurements of phosphodiester.
Time Frame
2 years
Title
Difference of membrane phosphomonoester alterations between UHR subjects and control subjects.
Description
Levels measurements of phosphomonoester.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria for the UHR group: Patient between 15 and 25 years old Patient fulfilling the UHR criteria objectified by the Comprehensive Assessment of At Risk Mental State scale (CAARMS) and by the social and professional functioning assessment scale (SOFAS) (the "Vulnerability" group is also taken into account, combining first-degree history and functional impact.) Patient with no contraindication to performing a 7T MRI examination Affiliated patient or beneficiary of a social security scheme. Free, informed consent, written and signed by the participant, the investigator and the legal representative if applicable (at the latest on the day of inclusion and before any examination required by the research). Inclusion Criteria for the Control group: Subjects aged 15 to 25 years old, healthy volunteer subject or subject to benefit from an imaging examination, not presenting the criteria of a mental health disorder objectified by a medical interview Subject with no contraindication to performing a 7T MRI examination Affiliated subject or beneficiary of a social security scheme. Free, informed and written consent signed by the participant, the investigator and the legal representative if applicable (at the latest on the day of inclusion and before any examination required by the research). Exclusion Criteria for the UHR group: Patient not at risk or already in a psychotic pathological process according to DSM-5 criteria. Patient already receiving antipsychotic treatment or whose background treatment was changed less than a month ago. Patient presenting an absolute contraindication to 7T MRI such as: foreign bodies (intracranial clips, vascular magnetic clips, cardiac or neural pacemakers, stents, coils, implantable chamber, intracorporeal metallic splinters, cochlear implants, intracorporeal metallic foreign bodies, mechanical heart valve, implanted injection pump, non-removable piercings), pregnant woman, allergy to contrast products, moderate to severe renal insufficiency, breastfeeding, implanted contraception, tinnitus, claustrophobia and braces. The relative contraindications are to be considered, namely: previous surgical interventions, medically implanted device, tattoo or permanent make-up. Exclusion criteria for the control group: - Subject presenting an absolute contraindication to 7T MRI such as: foreign bodies (intracranial clips, vascular magnetic clips, cardiac or neural pacemakers, stents, coils, implantable chamber, intracorporeal metallic fragments, cochlear implants, intracorporeal metallic foreign bodies, valve mechanical heart, implanted injection pump, non-removable piercings), pregnant woman, allergy to contrast products, moderate to severe renal insufficiency, breast-feeding, implanted contraception, tinnitus, claustrophobia and braces. The relative contraindications are to be considered, namely: previous surgical interventions, medically implanted device, tattoo or permanent make-up.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Richard HARY
Phone
0033 5 49 44 57 57
Email
richard.hary@ch-poitiers.fr
Facility Information:
Facility Name
Centre Hospitalier Henri Laborit
City
Poitiers
ZIP/Postal Code
86000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard HARY
Phone
0033 5 49 44 57 57
Email
richard.hary@ch-poitiers.fr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Evaluation of Membrane Phospholipid and Energy Metabolism in Subjects at High Risk of Psychotic Transition

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