The ATP Project (Antipsychotic-TEP-Psychosis)

NCT06651112 | Not Yet Recruiting

• 1 other identifier: 2025-5589
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to the early impacts of psychosis and antipsychotic medications on brain metabolism in young adults recently diagnosed with a first episode of psychosis. The main question aims to evaluate the effect of 4 to 6 weeks of antipsychotic medication on brain metabolism measured by PET scan (cerebral uptake of 11C-Acetoacetate + 18 Fluorodeoxyglucose). Participants will undergo a multimodal imaging protocol with other measures of psychopathology (e.g., cognition, depressive symptoms, etc.) and (metabolic marker, inflammation, etc).

Conditions

First Episose Psychosis; Metabolic Disease; Psychosis; Episode

Keywords

psychosis; cerebral metabolism; glucose; ketone; PET scan

Outcome Measures

Primary Outcomes (2)

• Cerebral metabolic rate of glucose and acetotacetate

  Cerebral metabolic rate of glucose and acetotacetate(μmol/100 g/min) quantified with PET scan with 18F-FDG tracer and 11C-AcAc

  BEFORE introduction of antipsychotic medicationand AFTER 4 to 6 weeks

• Net inflow of glucose and acetoacetate

  Net inflow of glucose and acetoacetate (k) as measured by PET scan with 18F-FDG and 11C-AcAc traceur (Kglu and Kacac, min-1)

  BEFORE introduction of antipsychotic medicationand AFTER 4 to 6 weeks

Secondary Outcomes (4)

• % of change in Brief Psychiatric Rating Scale

  BEFORE introduction of antipsychotic medicationand AFTER 4 to 6 weeks

• Concentration of glucose

  BEFORE introduction of antipsychotic medicationand AFTER 4 to 6 weeks

• Concentration of insuline

  BEFORE introduction of antipsychotic medicationand AFTER 4 to 6 weeks

• Concentration of Hemoglobin A1C

  BEFORE introduction of antipsychotic medicationand AFTER 4 to 6 weeks

Other Outcomes (8)

• Global brain volume measured by MRI

  BEFORE introduction of antipsychotic medicationand AFTER 4 to 6 weeks

• Thicknesses of the cerebral cortex

  BEFORE introduction of antipsychotic medicationand AFTER 4 to 6 weeks

• Depression status measured by the score of "Calgary Depression Scale for Schizophrenia

  BEFORE introduction of antipsychotic medicationand AFTER 4 to 6 weeks

Study Arms (1)

First episode psychosis

Individuals aged 18 to 35 from the Estrie region who have been evaluated by the "PEP team" (First episode psychosis intervention Team of the pschiatric department of the CIUSSS de l'Estrie-CHUS) and wish to start an antipsychotic (AP) for the treatment of a first episode of psychosis.

Drug: Antipsychotic drugs

Interventions

Antipsychotic drugs DRUG

Any Antipsychotic drugs prescripbe as standrd of care for this specific populaton

First episode psychosis

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Individuals aged 18 to 35 from the Estrie region who have been evaluated by the PEP team and wish to start an antipsychotic (AP) for the treatment of a first episode of psychosis.

You may qualify if:

• Admission to the PEP clinic in Estrie, either outpatient or inpatient, according to the transdiagnostic PEP model.
• Willingness to begin taking an AP (regardless of type and dose, or change in type and dose during the study).
• Ability to read and express themselves in French or English.
• Capable of understanding and signing consent.

You may not qualify if:

• Pregnancy, childbirth in the last 6 months, or breastfeeding.
• Presence of a metallic object in the body that is incompatible with MRI.
• Any use of APs for more than 2 continuous weeks in the past year and/or 6 weeks in a lifetime (except for aripiprazole if taken at less than 2.5 mg/day or quetiapine at less than 50 mg/day, regardless of duration or timing of the prescription).
• The following comorbidities: psychosis + borderline or intellectual disability, autism spectrum disorder, substance use disorder with decompensation, psychosis induced by a medical condition, or psychosis induced by drug use or withdrawal.
• Type 1 diabetes.
• Uncontrolled acute suicidal ideation.
• Other conditions that could interfere with participation according to the judgment of the qualified physician.

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Baszucki Brain Research Fund: collaborator

Study Sites (1)

Hotel-Dieu CIUSSS de l'Estrie-CHUS

Sherbrooke, Quebec, J1H 4C4, Canada

Location

Related Publications (15)

• Cunnane SC, Trushina E, Morland C, Prigione A, Casadesus G, Andrews ZB, Beal MF, Bergersen LH, Brinton RD, de la Monte S, Eckert A, Harvey J, Jeggo R, Jhamandas JH, Kann O, la Cour CM, Martin WF, Mithieux G, Moreira PI, Murphy MP, Nave KA, Nuriel T, Oliet SHR, Saudou F, Mattson MP, Swerdlow RH, Millan MJ. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020 Sep;19(9):609-633. doi: 10.1038/s41573-020-0072-x. Epub 2020 Jul 24.

  PMID: 32709961 BACKGROUND

• Croteau E, Castellano CA, Richard MA, Fortier M, Nugent S, Lepage M, Duchesne S, Whittingstall K, Turcotte EE, Bocti C, Fulop T, Cunnane SC. Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer's Disease. J Alzheimers Dis. 2018;64(2):551-561. doi: 10.3233/JAD-180202.

  PMID: 29914035 BACKGROUND

• Croteau E, Castellano CA, Fortier M, Bocti C, Fulop T, Paquet N, Cunnane SC. A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer's disease. Exp Gerontol. 2018 Jul 1;107:18-26. doi: 10.1016/j.exger.2017.07.004. Epub 2017 Jul 12.

  PMID: 28709938 BACKGROUND

• Agarwal SM, Kowalchuk C, Castellani L, Costa-Dookhan KA, Caravaggio F, Asgariroozbehani R, Chintoh A, Graff-Guerrero A, Hahn M. Brain insulin action: Implications for the treatment of schizophrenia. Neuropharmacology. 2020 May 15;168:107655. doi: 10.1016/j.neuropharm.2019.05.032. Epub 2019 May 29.

  PMID: 31152767 BACKGROUND

• Fortier M, Castellano CA, St-Pierre V, Myette-Cote E, Langlois F, Roy M, Morin MC, Bocti C, Fulop T, Godin JP, Delannoy C, Cuenoud B, Cunnane SC. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimers Dement. 2021 Mar;17(3):543-552. doi: 10.1002/alz.12206. Epub 2020 Oct 26.

  PMID: 33103819 BACKGROUND

• Andreasen NC, O'Leary DS, Flaum M, Nopoulos P, Watkins GL, Boles Ponto LL, Hichwa RD. Hypofrontality in schizophrenia: distributed dysfunctional circuits in neuroleptic-naive patients. Lancet. 1997 Jun 14;349(9067):1730-4. doi: 10.1016/s0140-6736(96)08258-x.

  PMID: 9193383 BACKGROUND

• Townsend L, Pillinger T, Selvaggi P, Veronese M, Turkheimer F, Howes O. Brain glucose metabolism in schizophrenia: a systematic review and meta-analysis of 18FDG-PET studies in schizophrenia. Psychol Med. 2023 Aug;53(11):4880-4897. doi: 10.1017/S003329172200174X. Epub 2022 Jun 22.

  PMID: 35730361 BACKGROUND

• Henkel ND, Wu X, O'Donovan SM, Devine EA, Jiron JM, Rowland LM, Sarnyai Z, Ramsey AJ, Wen Z, Hahn MK, McCullumsmith RE. Schizophrenia: a disorder of broken brain bioenergetics. Mol Psychiatry. 2022 May;27(5):2393-2404. doi: 10.1038/s41380-022-01494-x. Epub 2022 Mar 9.

  PMID: 35264726 BACKGROUND

• Lee J, Xue X, Au E, McIntyre WB, Asgariroozbehani R, Panganiban K, Tseng GC, Papoulias M, Smith E, Monteiro J, Shah D, Maksyutynska K, Cavalier S, Radoncic E, Prasad F, Agarwal SM, Mccullumsmith R, Freyberg Z, Logan RW, Hahn MK. Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures. Transl Psychiatry. 2024 Jan 10;14(1):19. doi: 10.1038/s41398-023-02716-8.

  PMID: 38199991 BACKGROUND

• Agarwal SM, Stogios N, Ahsan ZA, Lockwood JT, Duncan MJ, Takeuchi H, Cohn T, Taylor VH, Remington G, Faulkner GEJ, Hahn M. Pharmacological interventions for prevention of weight gain in people with schizophrenia. Cochrane Database Syst Rev. 2022 Oct 3;10(10):CD013337. doi: 10.1002/14651858.CD013337.pub2.

  PMID: 36190739 BACKGROUND

• Raben AT, Marshe VS, Chintoh A, Gorbovskaya I, Muller DJ, Hahn MK. The Complex Relationship between Antipsychotic-Induced Weight Gain and Therapeutic Benefits: A Systematic Review and Implications for Treatment. Front Neurosci. 2018 Jan 22;11:741. doi: 10.3389/fnins.2017.00741. eCollection 2017.

  PMID: 29403343 BACKGROUND

• Vancampfort D, Stubbs B, Mitchell AJ, De Hert M, Wampers M, Ward PB, Rosenbaum S, Correll CU. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry. 2015 Oct;14(3):339-47. doi: 10.1002/wps.20252.

  PMID: 26407790 BACKGROUND

• Sabe M, Pallis K, Solmi M, Crippa A, Sentissi O, Kaiser S. Comparative Effects of 11 Antipsychotics on Weight Gain and Metabolic Function in Patients With Acute Schizophrenia: A Dose-Response Meta-Analysis. J Clin Psychiatry. 2023 Feb 8;84(2):22r14490. doi: 10.4088/JCP.22r14490.

  PMID: 36752753 BACKGROUND

• Fan Z, Wu Y, Shen J, Ji T, Zhan R. Schizophrenia and the risk of cardiovascular diseases: a meta-analysis of thirteen cohort studies. J Psychiatr Res. 2013 Nov;47(11):1549-56. doi: 10.1016/j.jpsychires.2013.07.011. Epub 2013 Aug 15.

  PMID: 23953755 BACKGROUND

• Correll CU, Hojlund M, Graham C, Todtenkopf MS, McDonnell D, Simmons A. Weight Gain and Metabolic Changes in Patients With First-Episode Psychosis or Early-Phase Schizophrenia Treated With Olanzapine: A Meta-Analysis. Int J Neuropsychopharmacol. 2023 Jul 31;26(7):451-464. doi: 10.1093/ijnp/pyad029.

  PMID: 37326421 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma will be collected from whole blood sample.

MeSH Terms

Conditions

Metabolic Diseases; Psychotic Disorders; Ketosis

Interventions

Antipsychotic Agents

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Acidosis; Acid-Base Imbalance

Intervention Hierarchy (Ancestors)

Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Psychotropic Drugs

Study Officials

• Stephen Cunnane, Ph.D

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

• Kevin Zemmour, MD

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

• Maggie Hahn, MD

  University of Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melanie Fortier, M.Sc

CONTACT

8195758134; melanie.fortier2@usherbrooke.ca

Stephen Cunnane, Ph.D.

CONTACT

819-780-2220; melanie.fortier2@usherbrooke.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 11, 2024
• First Posted: October 21, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: November 8, 2024

Record last verified: 2024-11

Locations

CA (1)