Does GLP-1RA Prevent Deterioration of Metabolic State in Prediabetic and Diabetic Patients Treated With Antipsychotic Medication?

NCT04892199 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: SemaPsychiatry
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 3

Brief Summary

Background and objective: Clozapine and olanzapine are some of the most effective antipsychotic drugs, but unfortunately, both drugs induce weight gain and conveys a high degree of metabolic disturbances. The antipsychotic-induced side-effects cause a major clinical problem among patients diagnosed with schizophrenia receiving antipsychotic treatment. Limited effects have been demonstrated for counteracting the side-effects by the switch of antipsychotic therapy, non-pharmacological/behavioural interventions or adjunct pharmacological treatments. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA,) is approved for the treatment of type 2 diabetes worldwide. The objective of the study is to investigate effects of semaglutide once-weekly vs. semaglutide placebo once-weekly on the metabolic state in prediabetic or diabetic patients with schizophrenia, who have initiated treatment with clozapine or olanzapine. Methods and analysis: Trial design, intervention and participants: The study is a 26-week, double-blinded, randomized, parallel-group, placebo-controlled, good clinical practice (GCP)-monitored, clinical trial. 104 prediabetic or diabetic patients diagnosed with a schizophrenia, age 18 years and 65 years, who have initiated of clozapine- or olanzapine-treatment within 5 years will be included in the study. The patients will be randomized to receive blinded treatment in one of the two study arms; semaglutide once-weekly vs. semaglutide placebo. All participants who complete the 26 weeks of intervention, will be invited for a follow up visit 1.5 yeras after study completion. The primary endpoint is the change from baseline in glycated haemoglobin A1c (HbA1c). Secondary endpoints include change in body weight, hip and waist circumference, vitals, and plasma levels of insulin, glucose, C-peptid, insulin sensitivity, beta cell function, glucagon, liver function, lipid profile, incretin hormones, lipid profile, bone makers, body composition, bone density and proteomic analyses. Additional endpoints include alcohol, tobacco and drug use, food preferences, psychopathology, activity and quality of life.

Conditions

Metabolic Disturbance; Schizophrenia; Type 2 Diabetes; Clozapine; GLP-1; Olanzapine

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the change from baseline in glycated haemoglobin A1c (HbA1c).

  26 weeks

Secondary Outcomes (24)

• Body weight (Kg)

  26 weeks

• Hip and Waist circumference (Cm)

  26 weeks

• Incretin hormones (Blood sampling)

  26 weeks

• Bone Markers (Blood sampling)

  26 weeks

• Lipid Profile (Blood sampling)

  26 weeks

Study Arms (2)

Semaglutide injection once-weekly

ACTIVE COMPARATOR

Drug: Semaglutide, 1.34 mg/mL

Semaglutide-Placebo injection once-weekly

PLACEBO COMPARATOR

Drug: Semaglutide-placebo

Interventions

Semaglutide, 1.34 mg/mL DRUG

Semaglutide 1.34 mg/ml, 1.5 ml pre-filled pen-injector is supplied in pens for injection containing 2.0 mg of the GLP-1RA semaglutide in 1.5 ml sterile water with disodiumphosphate and propylenglycol, and phenol for conservation (pH 8.15). Direction for use will be given together with trial products.The possible doses of semaglutide are 0.25 mg, 0.50 mg and 1.0 mg. The initial weekly dose will be 0.25 mg for four weeks, then 0.5 mg for four weeks and then 1.0 mg for the remaining treatment period. Patients who, due to adverse events, do not tolerate up-titration to 1.0 mg semaglutide will remain on 0.5 mg once-weekly. The injection is administered subcutaneously once-weekly.

Semaglutide injection once-weekly

Semaglutide-placebo DRUG

The semaglutide placebo pens contain "XX-vehicle" (no active drug) and are administered in the same way and volume as semaglutide. The semaglutide placebo is specially packed for this study and will be used in the study only. The initial weekly dose will be 0.25 mg for four weeks, then 0.5 mg for four weeks and then 1.0 mg for the remaining treatment period. Patients who, due to adverse events, do not tolerate up-titration to 1.0 mg semaglutide placebo will remain on 0.5 mg once-weekly. The injection is administered once-weekly. If the lowest tolerated dose is less than 0.5 mg of semaglutide placebo once-weekly, the patient will be excluded from the study.

Semaglutide-Placebo injection once-weekly

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed oral and written consent
• Diagnosed with schizophrenia according to the criteria of ICD-10 (International Classification of Diseases, World Health Organization (WHO)) or the DSM-V (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the American Psychiatric Association)
• Initiating current treatment with clozapine or olanzapine within 60 months (not PRN ordinations)
• Age 18 years to 65 years (both included)
• Body mass index (BMI) ≥25 kg/m2
• Diagnosed with prediabetes or type 2 diabetes, after initiation of current treatment with clozapine- or olanzapine, with the following plasma levels: Prediabetes: HbA1c 35-47 mmol/mol or fasting plasma glucose (FPG) 5.6-6.9 mM or 2-h during 75 mg OGGT 7.8-11.0 mM. The test result has to be confirmed on a different day. Type 2 diabetes: HbA1c 48-57 mmol/mol or fasting plasma glucose (FPG) 6.9-9.9 mM or 2h OGTT \> 11 mM (although FPG and HbA1c might still be under the diagnostic range). The test result has to be confirmed on a different day.

You may not qualify if:

• Acute worsening of psychosis based on a clinical evaluation (score of 6 or 7 on the CGI-S scale)
• Coercive measures
• Females of child-bearing potential who are pregnant, breast-feeding or have intention of becoming pregnant.
• Women who are not willing to use adequate contraceptive during the full length of the study
• Patients treated with corticosteroids or other hormone therapy (except oestrogens)
• Any active substance abuse or dependence for the past six months (except for nicotine)
• Impaired hepatic function (plasma liver transaminases \>3 times upper normal limit)
• Impaired renal function (serum creatinine \>150 μmol/l and/or macroalbuminuria)
• Impaired pancreatic function (acute or chronic pancreatitis and/or plasma amylase \>2 times upper normal limit)
• Cardiac problems defined as decompensated heart failure (NYHA class III/IV), unstable angina pectoris and/or myocardial infarction within the last 12 months
• Hypertension with systolic blood pressure \>180 mmHg or diastolic blood pressure \>100 mmHg
• Any condition that the investigator feels would interfere with trial participation
• Receiving any experimental or pre-marketing drug within the last 3 months
• Use of weight-lowering pharmacotherapy within the preceding 3 month
• Known type 1 diabetes

Sponsors & Collaborators

• Anders Fink-Jensen, MD, DMSci: lead

Study Sites (3)

Psychosis Research Unit, Aarhus University Hospital, Psychiatry,

Aarhus, 8200, Denmark

Location

Psychiatric Centre Copenhagen, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Psychiatric Centre Nordsjaelland, Hillerød

Hillerød, 3400, Denmark

Location

Related Publications (2)

• Sass MR, Klausen MK, Schwarz CR, Rasmussen L, Giver MEB, Hviid M, Schilling C, Zamorski A, Jensen A, Gefke M, Storgaard H, Oturai PS, Kjaer A, Hartmann B, Holst JJ, Ekstrom CT, Vinberg M, Correll CU, Vilsboll T, Fink-Jensen A. Semaglutide and Early-Stage Metabolic Abnormalities in Individuals With Schizophrenia Spectrum Disorders: A Randomized Clinical Trial. JAMA Psychiatry. 2026 Feb 1;83(2):128-138. doi: 10.1001/jamapsychiatry.2025.3639.

  PMID: 41335431 DERIVED

• Sass MR, Danielsen AA, Kohler-Forsberg O, Storgaard H, Knop FK, Nielsen MO, Sjodin AM, Mors O, Correll CU, Ekstrom C, Vinberg M, Nielsen J, Vilsboll T, Fink-Jensen A. Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry). BMJ Open. 2023 Jan 31;13(1):e068652. doi: 10.1136/bmjopen-2022-068652.

  PMID: 36720576 DERIVED

MeSH Terms

Conditions

Schizophrenia; Diabetes Mellitus, Type 2

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Anders Fink-Jensen, MD

  Psychiatric Centre Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, DMSci

Model Details: Randomised, Double-blinded, Parallel, Placebo-controlled, clinical trial

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: May 19, 2021
• Study Start: September 1, 2021
• Primary Completion: March 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: September 25, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Researchers who provide a methodologically sound proposal

Locations

DK (3)