Gut Microbiome in AP Naive

NCT03414151 | Unknown

• 1 other identifier: 030/2017
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Antipsychotic (AP) medications are currently the cornerstone of treatment for schizophrenia (SCZ), with off-label prescription rapidly increasing in youth, with an established two-fold increase in standardized mortality ratio attributable to cardiovascular disease in this population. However, APs have been associated with common and serious metabolic adverse effects including weight gain and diabetes, to which youth are disproportionally vulnerable. The Gut Microbiome (GMB) has been suggested as a potential target warranting further study as a mechanism of AP induced weight gain and has also been linked directly with cognition and behavior. It is hypothesized that there will be changes in the gut microbiome overtime with treatment correlated with metabolic measures and that APs will produce changes in glucose tolerance, insulin sensitivity, adipokines, glucagon like peptide (GLP)-1, lipids, fasting glucose, body weight, and cognition.

Conditions

Psychotic Disorder; Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Change in Gut microbiome and DNA

  Patients will collect fecal samples at home using our well-established protocol at baseline, 6 weeks, and 12 weeks. Participants will be provided a kit containing a sterile specimen container and a cooling pad, as well as a stool collection tube for DNA analyses (OMNIgene•GUT, DNA Genotek Ottawa, ON). Patients will be instructed to transfer several grams of the feces into the specimen container and place the sample in the 2 bioharzard bags and then store in the freezer. On the day of their appointment they will transport the sample on the cooling pad (previously placed in the freezer) to their appointment. When the patient delivers the sample to the research staff, it will be immediately placed in a -80ºC freezer prior to being analyzed. These analyses with fecal samples will be conducted at McMaster University at the Farncombe Family Institute.

  12 weeks (baseline, week 6, week 12)

Secondary Outcomes (38)

• Oral glucose tolerance test

  12 weeks (baseline and week 12)

• Height

  12 weeks

• Weight

  12 weeks

• Blood pressure

  12 weeks

• Heart Rate

  12 weeks

Study Arms (2)

Observational - Case Arm

All participants will be placed in this arm or group if they have an eligible psychiatric diagnosis as a case (there is no randomization procedure)

Other: Observation

Observational - Healthy Control Arm

All participants will be placed in this arm if they are healthy controls (there is no randomization procedure)

Other: Observation

Interventions

Observation OTHER

No intervention administered.

Observational - Case Arm; Observational - Healthy Control Arm

Eligibility Criteria

• Age: 12 Years - 35 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Participants will include individuals who are either antipsychotic naïve or have not taken antipsychotics for at least 3 months prior to study participation. Participants will be between 12 and 35 years of age with a diagnosis of schizophrenia, schizoaffective disorder, or other specified schizophrenia spectrum and other psychotic disorder, as per DSM-V criteria.

You may qualify if:

• Ages 12-35
• Antipsychotic naïve or antipsychotic treatment for equal to or less than 2 weeks within the past 3 months; the minimum AP dose will be left to the discretion of the PI
• DSM-5 diagnosis (using SCID-IV-TR with supplemental questions from SCID-5 or SCID-5) of schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, and brief psychotic disorder, psychotic disorder NOS. and/or antipsychotic treatment for schizophrenia, schizoaffective disorder, or other specified schizophrenia spectrum and other psychotic disorder.

You may not qualify if:

• Previous antipsychotic treatment (greater than two weeks within the preceding 3 months)
• Presence of DSM-5 diagnosis which is not schizophrenia, schizoaffective disorder, or other specified schizophrenia spectrum and other psychotic disorder
• Use of any other medications for treatment of lipids, glucose, or weight as deemed to be clinically significant by the PI
• Use of other medications where the dose has changed within the past 6 weeks which are deemed by the PI to be clinically significant
• Pregnancy
• Eating disorder - active or previous
• Major medical or surgical event within the preceding 3 months
• Acute suicidal risk
• Irritable bowel disease, Crohn's disease, and/or diverticulitis/diverticulosis
• Type I diabetes, kidney/liver disease, and/or cancer
• Organ transplant
• Moderate to severe alcohol use , use of street drugs, and/or cannabis use (as deemed by PI)
• Immunosuppressants and/or anti-inflammatory medications
• Antibiotic/probiotic use within past 4 weeks
• Any other medical conditions or lifestyle habits deemed by the PI to impact the integrity of the sample/microbiota

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• McMaster University: collaborator

Study Sites (1)

Centre For Addiction and Mental Health

Toronto, Ontario, M5T1R8, Canada

RECRUITING

Related Publications (4)

• Hennekens CH, Hennekens AR, Hollar D, Casey DE. Schizophrenia and increased risks of cardiovascular disease. Am Heart J. 2005 Dec;150(6):1115-21. doi: 10.1016/j.ahj.2005.02.007.

  PMID: 16338246 BACKGROUND

• Gold SM, Dziobek I, Sweat V, Tirsi A, Rogers K, Bruehl H, Tsui W, Richardson S, Javier E, Convit A. Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes. Diabetologia. 2007 Apr;50(4):711-9. doi: 10.1007/s00125-007-0602-7. Epub 2007 Feb 14.

  PMID: 17334649 BACKGROUND

• Letourneau G, Bentaleb LA, Stip B, Luck D, Stip E. Relationships between Brain Structure and Metabolic Changes in Schizophrenia Patients Treated with Olanzapine: A Voxel-Based Morphometric Study. Schizophr Res Treatment. 2011;2011:862350. doi: 10.1155/2011/862350. Epub 2011 May 25.

  PMID: 22937275 BACKGROUND

• Bora E, Akdede BB, Alptekin K. The relationship between cognitive impairment in schizophrenia and metabolic syndrome: a systematic review and meta-analysis. Psychol Med. 2017 Apr;47(6):1030-1040. doi: 10.1017/S0033291716003366. Epub 2016 Dec 29.

  PMID: 28032535 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood serum; fecal sample (collected in OMNIgene•GUT, DNA Genotek Ottawa, ON)

MeSH Terms

Conditions

Psychotic Disorders; Schizophrenia

Interventions

Observation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Margaret K Hahn, PhD, MD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicole MacKenzie, M.Ed

CONTACT

4165358501; nicole.mackenzie@camh.ca

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician/Scientist

Study Record Dates

• First Submitted: October 28, 2017
• First Posted: January 29, 2018
• Study Start: February 7, 2018
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: July 26, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)