Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04892199
Other study ID # SemaPsychiatry
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
Start date September 1, 2021
Est. completion date December 31, 2024

Study information

Verified date October 2023
Source Psychiatric Centre Rigshospitalet
Contact Anders Fink-Jensen, MD
Phone +45 22755843
Email anders.fink-jensen@regionh.dk
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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. 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 104
Est. completion date December 31, 2024
Est. primary completion date July 1, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: 1. Informed oral and written consent 2. 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) 3. Initiating current treatment with clozapine or olanzapine within 60 months (not PRN ordinations) 4. Age 18 years to 65 years (both included) 5. Body mass index (BMI) =25 kg/m2 6. 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. Exclusion Criteria: 1. Acute worsening of psychosis based on a clinical evaluation (score of 6 or 7 on the CGI-S scale) 2. Coercive measures 3. Females of child-bearing potential who are pregnant, breast-feeding or have intention of becoming pregnant. 4. Women who are not willing to use adequate contraceptive during the full length of the study 5. Patients treated with corticosteroids or other hormone therapy (except oestrogens) 6. Any active substance abuse or dependence for the past six months (except for nicotine) 7. Impaired hepatic function (plasma liver transaminases >3 times upper normal limit) 8. Impaired renal function (serum creatinine >150 µmol/l and/or macroalbuminuria) 9. Impaired pancreatic function (acute or chronic pancreatitis and/or plasma amylase >2 times upper normal limit) 10. Cardiac problems defined as decompensated heart failure (NYHA class III/IV), unstable angina pectoris and/or myocardial infarction within the last 12 months 11. Hypertension with systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg 12. Any condition that the investigator feels would interfere with trial participation 13. Receiving any experimental or pre-marketing drug within the last 3 months 14. Use of weight-lowering pharmacotherapy within the preceding 3 month 15. Known type 1 diabetes 16. Suicidal behavior as judged by the investigator and based on clinical evaluation. At all contact with patient attendance possible suicidality will be evaluated according to the guidelines. If the patient is evaluated as suicidal, the person will be excluded from the study and evaluated by a senior consultant in psychiatry, who will take further action. 17. Plasma HbA1c > 57 mmol/mol (tested twice) in which case the patient will be excluded from the study and transferred to general practitioner or hospital for diabetic treatment. No diabetic medication is allowed except for the trial medicin. 18. Any known contraindication towards the treatment with semaglutide.

Study Design


Intervention

Drug:
Semaglutide, 1.34 mg/mL
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-placebo
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.

Locations

Country Name City State
Denmark Psychosis Research Unit, Aarhus University Hospital, Psychiatry, Aarhus
Denmark Psychiatric Centre Copenhagen, Rigshospitalet Copenhagen
Denmark Psychiatric Centre Nordsjaelland, Hillerød Hillerød

Sponsors (1)

Lead Sponsor Collaborator
Anders Fink-Jensen, MD, DMSci

Country where clinical trial is conducted

Denmark, 

Outcome

Type Measure Description Time frame Safety issue
Primary The primary endpoint is the change from baseline in glycated haemoglobin A1c (HbA1c). 26 weeks
Secondary Body weight (Kg) 26 weeks
Secondary Hip and Waist circumference (Cm) 26 weeks
Secondary Incretin hormones (Blood sampling) GLP-1, GLP-2 and GIP 26 weeks
Secondary Bone Markers (Blood sampling) Calcitonin, Vit-D, Ca, Phosphate, Mg, PTH, PINP, CTX, OC 26 weeks
Secondary Lipid Profile (Blood sampling) LDL, HDL, triglycerider, total kolesterol, 26 weeks
Secondary Hormones (blood sampling) Insulin, glucagon and C-peptide 26 weeks
Secondary Visceral fat DXA scanning 26 weeks
Secondary Android to Gynoid fat ratio DXA scanning 26 weeks
Secondary Total body fat DXA scanning 26 weeks
Secondary Bone density DXA scanning 26 weeks
Secondary Psychopathology PANSS-6 interview 26 weeks
Secondary Registration of body movements/level of activity with a sensor Activity measurements (approximate for sleep, inactivity, energy expenditure and steps taken by the patient) will be collected continuously by the use of a wearable activity device worn by the patient for 1 week from inclusion day and 1 week at the end of the study 26 weeks
Secondary Reward value of sweet and fatty candy Clicker test 26 weeks
Secondary Alcohol use Questionnaires: AUDIT 26 weeks
Secondary Tobacco use Questionnaires: FNTD 26 weeks
Secondary Drug use Questionnaires: DUDIT 26 weeks
Secondary Schizophrenia quality of life scale Questionnaire: SQLS 26 weeks
Secondary Psychosocial disability Rating GAPD 26 weeks
Secondary Liver function (blood sampling) ALT, ALP, AST, trombocytes and bilirubin 26 weeks
Secondary Proteomic analyses (Blood sampling) Inflammatory biomarkers and cytokines: IFN-?, TNF-a, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, MDA, plasma antioxidants uric acid and, vitaminC 26 weeks
Secondary Proteomic analyses (Urine sampling) biomarkers for measurement of systemic oxidative stress on DNA and RNA: 8-oxo-7,8-dihydro2´-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo 26 weeks
Secondary FIB-4 score A non-invasive scoring system for Liver Fibrosis is a non-invasive scoring system based on several laboratory tests (ALT, AST, trombocytes) and age 26 weeks
Secondary Vitals Blood pressure and pulse 26 weeks
Secondary Insulin sensitivity and beta cell function evaluated by homeostatic model assessment 26 weeks
See also
  Status Clinical Trial Phase
Recruiting NCT05039489 - A Study on the Brain Mechanism of cTBS in Improving Medication-resistant Auditory Hallucinations in Schizophrenia N/A
Completed NCT05111548 - Brain Stimulation and Cognitive Training - Efficacy N/A
Completed NCT05321602 - Study to Evaluate the PK Profiles of LY03010 in Patients With Schizophrenia or Schizoaffective Disorder Phase 1
Completed NCT04503954 - Efficacy of Chronic Disease Self-management Program in People With Schizophrenia N/A
Completed NCT02831231 - Pilot Study Comparing Effects of Xanomeline Alone to Xanomeline Plus Trospium Phase 1
Completed NCT05517460 - The Efficacy of Auricular Acupressure on Improving Constipation Among Residents in Community Rehabilitation Center N/A
Completed NCT03652974 - Disturbance of Plasma Cytokine Parameters in Clozapine-Resistant Treatment-Refractory Schizophrenia (CTRS) and Their Association With Combination Therapy Phase 4
Recruiting NCT04012684 - rTMS on Mismatch Negativity of Schizophrenia N/A
Recruiting NCT04481217 - Cognitive Factors Mediating the Relationship Between Childhood Trauma and Auditory Hallucinations in Schizophrenia N/A
Completed NCT00212784 - Efficacy and Safety of Asenapine Using an Active Control in Subjects With Schizophrenia or Schizoaffective Disorder (25517)(P05935) Phase 3
Completed NCT04092686 - A Clinical Trial That Will Study the Efficacy and Safety of an Investigational Drug in Acutely Psychotic People With Schizophrenia Phase 3
Completed NCT01914393 - Pediatric Open-Label Extension Study Phase 3
Recruiting NCT03790345 - Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics Phase 2/Phase 3
Recruiting NCT05956327 - Insight Into Hippocampal Neuroplasticity in Schizophrenia by Investigating Molecular Pathways During Physical Training N/A
Terminated NCT03261817 - A Controlled Study With Remote Web-based Adapted Physical Activity (e-APA) in Psychotic Disorders N/A
Terminated NCT03209778 - Involuntary Memories Investigation in Schizophrenia N/A
Completed NCT02905604 - Magnetic Stimulation of the Brain in Schizophrenia or Depression N/A
Recruiting NCT05542212 - Intra-cortical Inhibition and Cognitive Deficits in Schizophrenia N/A
Completed NCT04411979 - Effects of 12 Weeks Walking on Cognitive Function in Schizophrenia N/A
Terminated NCT03220438 - TMS Enhancement of Visual Plasticity in Schizophrenia N/A