Back to resultsDoes GLP-1RA Prevent Deterioration of Metabolic State in Prediabetic and Diabetic Patients Treated With Antipsychotic Medication?
Primary Purpose
Metabolic Disturbance, Schizophrenia, Type 2 Diabetes
Status
Recruiting
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Semaglutide, 1.34 mg/mL
Semaglutide-placebo
Sponsored by
About this trial
This is an interventional treatment trial for Metabolic Disturbance
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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 >2 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
- 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.
- 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.
- Any known contraindication towards the treatment with semaglutide.
Sites / Locations
- Psychosis Research Unit, Aarhus University Hospital, Psychiatry,
- Psychiatric Centre Copenhagen, RigshospitaletRecruiting
- Psychiatric Centre Nordsjaelland, HillerødRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Semaglutide injection once-weekly
Semaglutide-Placebo injection once-weekly
Arm Description
Outcomes
Primary Outcome Measures
The primary endpoint is the change from baseline in glycated haemoglobin A1c (HbA1c).
Secondary Outcome Measures
Body weight (Kg)
Hip and Waist circumference (Cm)
Incretin hormones (Blood sampling)
GLP-1, GLP-2 and GIP
Bone Markers (Blood sampling)
Calcitonin, Vit-D, Ca, Phosphate, Mg, PTH, PINP, CTX, OC
Lipid Profile (Blood sampling)
LDL, HDL, triglycerider, total kolesterol,
Hormones (blood sampling)
Insulin, glucagon and C-peptide
Visceral fat
DXA scanning
Android to Gynoid fat ratio
DXA scanning
Total body fat
DXA scanning
Bone density
DXA scanning
Psychopathology
PANSS-6 interview
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
Reward value of sweet and fatty candy
Clicker test
Alcohol use
Questionnaires: AUDIT
Tobacco use
Questionnaires: FNTD
Drug use
Questionnaires: DUDIT
Schizophrenia quality of life scale
Questionnaire: SQLS
Psychosocial disability
Rating GAPD
Liver function (blood sampling)
ALT, ALP, AST, trombocytes and bilirubin
Proteomic analyses (Blood sampling)
Inflammatory biomarkers and cytokines: IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, MDA, plasma antioxidants uric acid and, vitaminC
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
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
Vitals
Blood pressure and pulse
Insulin sensitivity and beta cell function
evaluated by homeostatic model assessment
Full Information
NCT ID
NCT04892199
First Posted
March 1, 2021
Last Updated
October 6, 2023
Sponsor
Anders Fink-Jensen, MD, DMSci
1. Study Identification
Unique Protocol Identification Number
NCT04892199
Brief Title
Does GLP-1RA Prevent Deterioration of Metabolic State in Prediabetic and Diabetic Patients Treated With Antipsychotic Medication?
Official Title
Does the Glucagon-like Peptide-1 Receptor Agonist Semaglutide Prevent Deterioration of Metabolic State in Prediabetic or Diabetic Patients With Schizophrenia Treated With the Antipsychotic Compounds Clozapine or Olanzapine?
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2021 (Actual)
Primary Completion Date
July 1, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Anders Fink-Jensen, MD, DMSci
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Disturbance, Schizophrenia, Type 2 Diabetes, Clozapine, GLP-1, Olanzapine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Randomised, Double-blinded, Parallel, Placebo-controlled, clinical trial
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
104 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Semaglutide injection once-weekly
Arm Type
Active Comparator
Arm Title
Semaglutide-Placebo injection once-weekly
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Semaglutide, 1.34 mg/mL
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Semaglutide-placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
The primary endpoint is the change from baseline in glycated haemoglobin A1c (HbA1c).
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Body weight (Kg)
Time Frame
26 weeks
Title
Hip and Waist circumference (Cm)
Time Frame
26 weeks
Title
Incretin hormones (Blood sampling)
Description
GLP-1, GLP-2 and GIP
Time Frame
26 weeks
Title
Bone Markers (Blood sampling)
Description
Calcitonin, Vit-D, Ca, Phosphate, Mg, PTH, PINP, CTX, OC
Time Frame
26 weeks
Title
Lipid Profile (Blood sampling)
Description
LDL, HDL, triglycerider, total kolesterol,
Time Frame
26 weeks
Title
Hormones (blood sampling)
Description
Insulin, glucagon and C-peptide
Time Frame
26 weeks
Title
Visceral fat
Description
DXA scanning
Time Frame
26 weeks
Title
Android to Gynoid fat ratio
Description
DXA scanning
Time Frame
26 weeks
Title
Total body fat
Description
DXA scanning
Time Frame
26 weeks
Title
Bone density
Description
DXA scanning
Time Frame
26 weeks
Title
Psychopathology
Description
PANSS-6 interview
Time Frame
26 weeks
Title
Registration of body movements/level of activity with a sensor
Description
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
Time Frame
26 weeks
Title
Reward value of sweet and fatty candy
Description
Clicker test
Time Frame
26 weeks
Title
Alcohol use
Description
Questionnaires: AUDIT
Time Frame
26 weeks
Title
Tobacco use
Description
Questionnaires: FNTD
Time Frame
26 weeks
Title
Drug use
Description
Questionnaires: DUDIT
Time Frame
26 weeks
Title
Schizophrenia quality of life scale
Description
Questionnaire: SQLS
Time Frame
26 weeks
Title
Psychosocial disability
Description
Rating GAPD
Time Frame
26 weeks
Title
Liver function (blood sampling)
Description
ALT, ALP, AST, trombocytes and bilirubin
Time Frame
26 weeks
Title
Proteomic analyses (Blood sampling)
Description
Inflammatory biomarkers and cytokines: IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, MDA, plasma antioxidants uric acid and, vitaminC
Time Frame
26 weeks
Title
Proteomic analyses (Urine sampling)
Description
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
Time Frame
26 weeks
Title
FIB-4 score
Description
A non-invasive scoring system for Liver Fibrosis is a non-invasive scoring system based on several laboratory tests (ALT, AST, trombocytes) and age
Time Frame
26 weeks
Title
Vitals
Description
Blood pressure and pulse
Time Frame
26 weeks
Title
Insulin sensitivity and beta cell function
Description
evaluated by homeostatic model assessment
Time Frame
26 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
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.
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.
Any known contraindication towards the treatment with semaglutide.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anders Fink-Jensen, MD
Phone
+45 22755843
Email
anders.fink-jensen@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Marie Reeberg Sass, MD
Phone
+45 40217486
Email
marie.reeberg.sass@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anders Fink-Jensen, MD
Organizational Affiliation
Psychiatric Centre Copenhagen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Psychosis Research Unit, Aarhus University Hospital, Psychiatry,
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Aalkjaer Danielsen, MD
First Name & Middle Initial & Last Name & Degree
Marie Reeberg Sass, MD
Email
marie.reeberg.sass@regionh.dk
Facility Name
Psychiatric Centre Copenhagen, Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anders Fink-Jensen, Professor, Dmsc,
Phone
+4538647072
Email
anders.fink-jensen@regionh.dk
First Name & Middle Initial & Last Name & Degree
Marie Reeberg Sass, MD
Email
marie.reeberg.sass@regionh.dk
Facility Name
Psychiatric Centre Nordsjaelland, Hillerød
City
Hillerød
ZIP/Postal Code
3400
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maj Vinberg, MD
Email
maj.vinberg@regionh.dk
First Name & Middle Initial & Last Name & Degree
Marie Reeberg Sass, MD
Email
marie.reeberg.sass@regionh.dk
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All of the individual participant data collected during the trial, after deidentification.
IPD Sharing Time Frame
Immediately following publication. No end date.
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal
Learn more about this trial
Does GLP-1RA Prevent Deterioration of Metabolic State in Prediabetic and Diabetic Patients Treated With Antipsychotic Medication?
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