Home-based Intervention With Semaglutide Treatment Of Neuroleptica-Related Prediabetes

NCT05193578 | Completed Phase 2 DMC

• 1 other identifier: Eudra CT 2020-004374-22
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate whether the Glucagon Like Peptide 1 (GLP-1) Semaglutide (1.34 mg/ml) has preventive effect compared to placebo in the development of diabetes and Metabolic Syndrome in people with pre-diabetes, overweight and schizophrenia, who receive antipsychotic treatment. Furthermore to investigate for an effect of Semaglutide compared to placebo on psychotic symptoms and quality of life in people with schizophrenia, prediabetes and overweight.

Conditions

Schizophrenia; Prediabetic State

Keywords

Randomized Controlled Trial; Metabolic Syndrome; Overweight; Glucagon-Like Peptide 1; Cardiovascular Diseases; Positive and negative symptoms (PANSS); Quality of Life

Outcome Measures

Primary Outcomes (1)

• HbA1c (mmol/mol)

  Absolute change in HbA1c reported as mmol/mol from baseline to end of treatment

  30 weeks

Secondary Outcomes (16)

• Weight

  30 weeks

• Height

  30 weeks

• Chaneges in body mass index (BMI)

  30 weeks

• Waist circumference (cm)

  30 weeks

• Glycemic status (blood sampling)

  30 weeks

Study Arms (2)

Semaglutide

ACTIVE COMPARATOR

Active Comparator: Semaglutide injection once-weekly The participants start with Semaglutide given as 0.25 mg subcutaneously per week for 4 weeks. Then, the dose is uptitrated to 0.5 mg subcutaneously per week for 4 weeks, whereafter the highest dose is reached: 1 mg subcutaneously per week until the end of the study (week 30). Subjects, who experience side effects that hinder a stepwise increase in study drug, will remain at the highest possible tolerated dose for the rest of the study.

Drug: Semaglutide, 1.34 mg/mL

Placebo

PLACEBO COMPARATOR

Semaglutide-Placebo injections once weekly. The Semaglutide-Placebo pens are produced by Novo Nordisk A/S and resemble the pens containing active drug. Semaglutide-Placebo pens contain vehicle, i.e. no active drug. Semaglutide-Placebo is administered similarly to semaglutide. That is using the same uptitration regime and volume as the active comparator, Semaglutide. Subjects, who experience side effects that hinder a stepwise increase in Semaglutide-Placebo, will remain at the highest possible tolerated dose for the rest of the study.

Other: Placebo

Interventions

Semaglutide, 1.34 mg/mL DRUG

Semaglutide, 1.34 mg/mL

Semaglutide

Placebo OTHER

Semaglutide-Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosed with schizophrenia spectrum disorder (ICD10 codes DF20, DF21 or DF25)
• Age between 18 and 60 years (both included)
• Approved contraception for female participants
• Treated by one of the OPUS clinics and or community psychiatry centers teams and community psychiatry in the Region of Southern Denmark or Zealand
• Antipsychotic SGA treatment for at least 6 months
• Stable co-medication for at least 1 month
• HbA1c between 39-47 mmol/mol (both included). Two measurements with ≥3 month interval are required to confirm prediabetes. The first measurement is identified and obtained from patient journals, the second prior to enrolment
• BMI ≥27 kg/m2. Two weights with ≥3 month interval are required to confirm obesity
• Capable of providing informed oral and written consent

You may not qualify if:

• Diagnosis of diabetes (T1D or T2D) or a HbA1c \>47 mmol/mol
• Active malignant disease within the last 5 years
• Pregnancy or breast feeding
• Exceeding high risk consumption limit (\>21 / 14 units of alcohol for men / women, respectively) or severe substance abuse
• Unwillingness to allow home visits by a study nurse
• Significant somatic disease: 1) end-stage renal failure (eGFR \<15 ml/min); 2) elevated liver function tests (liver transaminases \>2 times upper normal limit); 3) history of acute or chronic pancreatitis; 4) heart failure (NYHA class IV) or unstable angina pectoris or myocardial infarction with the last 6 months; 5) uncontrolled hypertension (systolic blood pressure \>180 mm Hg, diastolic blood pressure \>100 mm Hg)
• Previous treatment with study drug or use of other weight reducing drugs within the last 6 month
• Participation in other drug trials
• Treatment with drugs approved for overt diabetes type 2. (Metformin not included)
• Circumstances that the investigator believes will interfere with the trial

Sponsors & Collaborators

• Jan Frystyk: lead
• Region Zealand: collaborator
• Region of Southern Denmark: collaborator
• Steno Diabetes Center Sjaelland: collaborator
• Steno Diabetes Center Odense: collaborator

Study Sites (1)

Odense University Hospital

Odense, Denmark

Location

Related Publications (2)

• Ganeshalingam AA, Uhrenholt N, Arnfred S, Gaede P, During S, Stenager EN, Bunger N, Pedersen AK, Bilenberg N, Frystyk J. Semaglutide Treatment of Antipsychotic-Treated Patients With Schizophrenia, Prediabetes, and Obesity: The HISTORI Randomized Clinical Trial. JAMA Psychiatry. 2025 Nov 1;82(11):1065-1074. doi: 10.1001/jamapsychiatry.2025.2332.

  PMID: 40900607 DERIVED

• Ganeshalingam AA, Uhrenholt NG, Arnfred S, Gaede PH, Bilenberg N, Frystyk J. Home-based Intervention with Semaglutide Treatment of Neuroleptic-Related Prediabetes (HISTORI): protocol describing a prospective, randomised, placebo controlled and double-blinded multicentre trial. BMJ Open. 2024 Mar 18;14(3):e077173. doi: 10.1136/bmjopen-2023-077173.

  PMID: 38503415 DERIVED

MeSH Terms

Conditions

Schizophrenia; Prediabetic State; Metabolic Syndrome; Overweight; Cardiovascular Diseases

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; Insulin Resistance; Hyperinsulinism; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jan Frystyk, Professor

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The un-blinding will occur after the data analysis have ended and two blinded conclusions have been uploaded to clinicaltrials.gov based on the results of the primary and secondary outcomes defined in the SAP. The two blinded conclusions are added to the SAP.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 9, 2021
• First Posted: January 18, 2022
• Study Start: January 1, 2022
• Primary Completion: March 18, 2024
• Study Completion: May 1, 2024
• Last Updated: July 8, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 15 years
• Access Criteria: In case there is a need for further studies of biomaterial, application will again be made to the Science Ethics Committee.

Locations

DK (1)