Does a GLP-1 Receptor Agonist Change Glucose Tolerance in Antipsychotic-treated Patients? (GREAT)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University Hospital, Gentofte, Copenhagen
University of Cambridge
Information provided by (Responsible Party):
Anders Fink-Jensen, MD, DMSci, Psychiatric Centre Rigshospitalet
ClinicalTrials.gov Identifier:
NCT01845259
First received: April 14, 2013
Last updated: March 11, 2016
Last verified: March 2016

April 14, 2013
March 11, 2016
April 2013
March 2016   (final data collection date for primary outcome measure)
Glucose tolerance [ Time Frame: Baseline - 16 weeks ] [ Designated as safety issue: No ]
Change in Glucose tolerance (measured by area under the curve (AUC) for plasma glucose (PG) excursion following a 4-hour 75 g Oral Glucose Tolerance Test (OGTT))
Same as current
Complete list of historical versions of study NCT01845259 on ClinicalTrials.gov Archive Site
  • Dysglycaemia [ Time Frame: Baseline - 16 weeks ] [ Designated as safety issue: No ]
    Change in dysglycaemia (Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT), combined IFG/IGT or diabetes)
  • Body weight [ Time Frame: Every 4 weeks from baseline - 16 weeks ] [ Designated as safety issue: No ]
  • Secretion of incretin hormons, insulin sensitivity and beta cell function [ Time Frame: Baseline - 16 weeks ] [ Designated as safety issue: No ]
    Evaluated by Homeostatic Model of Assessment (HOMA)
  • Body composition [ Time Frame: Baseline - 16 weeks ] [ Designated as safety issue: No ]
    Dual energy x-ray absorptiometry (DEXA)-scan
  • Lipid profile and liver function [ Time Frame: Every 4 weeks from baseline - 16 weeks ] [ Designated as safety issue: No ]
    Blood sample
  • Psychopathology [ Time Frame: Baseline - 16 weeks ] [ Designated as safety issue: No ]
    Schizophrenia Quality of Life Scale (SQLS), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement (CGI-I), Global Assessment of Function (GAF)
  • Waist circumference [ Time Frame: Every 4 weeks from baseline - 16 weeks ] [ Designated as safety issue: No ]
  • Blood pressure [ Time Frame: Every 4 weeks from baseline - 16 weeks ] [ Designated as safety issue: No ]
Same as current
  • Alcohol use [ Time Frame: Every 4 weeks from baseline - 16 weeks ] [ Designated as safety issue: No ]
    AUDIT (Alcohol Use Disorder Identification Test)
  • Changes i dietary and exercise records [ Time Frame: Every 4 weeks from baseline - 16 weeks ] [ Designated as safety issue: No ]
  • Proteomic fingerprinting [ Time Frame: Every 4 weeks from baseline - 16 weeks ] [ Designated as safety issue: No ]
    We wish to identify baseline imbalances among our participants with proteomic fingerprinting. Furthermore, we will test the dysglycemic and metabolic disturbances in patients treated for 16 weeks with liraglutide or placebo. We wish to investigate, whether treatment with liraglutide possible could rebalance some of the metabolic, immune and hormonal disturbances, we expect to find at baseline.
  • Long term follow-up 52 weeks after end of participation [ Time Frame: 52 weeks after 16 weeks of liraglutide/placebo-treatment ] [ Designated as safety issue: No ]

    The follow-up 52 weeks after end of participation will include:

    • Medical history: Changes in antipsychotic medication Changes in other medications Changes in diet and exercise habits Changes in smoking Diagnosed with diabetes or other diseases

    • Blood sampling
    • Blood pressure
    • Weight
    • Height
    • Waist circumference
    • Alcohol Use Disorder Identification Test (AUDIT)
    • Schizophrenia Quality of Life Scale (SQLS)
    • Clinical Global Impression-Severity and Improvement (CGI-S+I)
    • Global Assessment of Function (GAF)
  • Baseline comparisons with healthy controls (non-psychiatric, non-diabetic) [ Time Frame: Baseline examination ] [ Designated as safety issue: No ]
    In order to identify risk factors for diabetes development in individuals on antipsychotic medications, the baseline examinations will be performed on a group of healthy controls without psychiatric illnes or pre-diabetes (n=10). The healthy controls will be matched to our participants in regards to gender, age and BMI.
  • Alcohol use [ Time Frame: Every 4 weeks from baseline - 16 weeks ] [ Designated as safety issue: No ]
    AUDIT (Alcohol Use Disorder Identification Test)
  • Changes i dietary and exercise records [ Time Frame: Every 4 weeks from baseline - 16 weeks ] [ Designated as safety issue: No ]
 
Does a GLP-1 Receptor Agonist Change Glucose Tolerance in Antipsychotic-treated Patients?
Does a GLP-1 Receptor Agonist Change Glucose Tolerance in Antipsychotic-treated Patients? A Randomized, Double-blinded, Placebo-controlled Clinical Trial
Metabolic disturbances, obesity and life-shortening cardiovascular morbidity are major clinical problems among antipsychotic-treated patients. Especially two of the most efficacious antipsychotics, clozapine and olanzapine, cause weight gain and metabolic disturbances and can rarely be replaced by other drugs due to the effectiveness of the compounds. Glucagon-like peptide 1 (GLP-1) has improved glycemic control among patients with type 2 diabetes. The study will investigate whether the beneficial effects of GLP-1 analogues on glycemic control in type 2 diabetic patients, can be extended to a population of non-diabetic, dysglycemic psychiatric patients, receiving antipsychotic medical treatment.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Impaired Glucose Tolerance Associated With Drugs
  • Drug: Liraglutide
    Once a day 1,8 mg subcutaneous injection for 16 weeks
    Other Names:
    • Victoza
    • GLP-1 agonist
  • Drug: Liraglutide Placebo
    Once a day 1,8 mg subcutaneous injection for 16 weeks
    Other Name: Placebo
  • Experimental: Liraglutide
    Once a day 1,8 mg subcutaneous injection for 16 weeks
    Intervention: Drug: Liraglutide
  • Placebo Comparator: Liraglutide placebo
    Once a day 1,8 mg subcutaneous injection for 16 weeks
    Intervention: Drug: Liraglutide Placebo
Sharma AN, Ligade SS, Sharma JN, Shukla P, Elased KM, Lucot JB. GLP-1 receptor agonist liraglutide reverses long-term atypical antipsychotic treatment associated behavioral depression and metabolic abnormalities in rats. Metab Brain Dis. 2015 Apr;30(2):519-27. doi: 10.1007/s11011-014-9591-7. Epub 2014 Jul 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
103
March 2017
March 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Informed oral and written consent
  • Diagnosed with schizophrenia, schizotypal disorder or paranoid psychosis according to the criteria of ICD10 (International Classification of Diseases, World Health Organization) or the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the American Psychiatric Association)
  • and on stable antipsychotic treatment with either clozapine or olanzapine for at least 6 months (without dose change for at least 30 days)
  • Stable co-medications for at least 30 days.
  • Age ≥18 years and ≤65 years
  • Stable weight (defined as less than 5% change in weight over the last 3 month before inclusion)
  • BMI ≥27 kg/m2
  • Dysglycaemia (IFG, i.e. fasting plasma glucose level from 6.1 mmol/L to 6.9 mmol/L or IGT, i.e. two-hour glucose levels > 7.8 mmol/L on the 75-g oral glucose tolerance test with a fasting plasma glucose of less than 7.0 mmol/L and HbA1c < 48 mmol/mol or HbA1c: 43 mmol/mol ≤ HbA1c ≤ 47 mmol/mol)

Exclusion Criteria:

  • Compulsory treatment
  • Females of child bearing potential who are pregnant, breast-feeding or have intention of becoming pregnant or are not using adequate contraceptive measures
  • Subjects treated with corticosteroids or other hormone therapy (except estrogens)
  • Any active substance abuse or dependence for the past 6 months (except for nicotine)
  • Impaired hepatic function (liver transaminases >2 times upper normal limit)
  • Impaired renal function (se-creatinine >150 μM and/or macroalbuminuria)
  • Impaired pancreatic function (acute or chronic pancreatitis and/or amylase >2 times upper normal limit)
  • Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris and/or myocardial infarction within the last 12 months
  • Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >100 mmHg)
  • Any condition that the investigator feels would interfere with trial participation
  • Receiving any investigational drug within the last 3 months
  • Use of weight-lowering pharmacotherapy within the preceding 3 month
  • Type 1 or 2 diabetes with HbA1c > 6.5%

Also a group of healthy controls (n=10) will have the baseline examinations done. The healthy controls will be matched to our participants in regards to gender, BMI and age. The same inclusion and exclusion criteria will apply for these controls, except these participants are not allowed to have known psychiatric illness, receive anti-psychotic medications, or have a family history of type 2 diabetes (2 generations).

Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT01845259
GLP-1 antipsychotics, 2013-000121-31, U1111-1128-3404
Yes
Not Provided
Not Provided
Anders Fink-Jensen, MD, DMSci, Psychiatric Centre Rigshospitalet
Psychiatric Centre Rigshospitalet
  • University Hospital, Gentofte, Copenhagen
  • University of Cambridge
Principal Investigator: Anders Fink-Jensen, MD, DMSci Psychiatric Centre Rigshospitalet
Principal Investigator: Tina Vilsbøll, MD, DMSci Diabetes Research Division, Gentofte
Psychiatric Centre Rigshospitalet
March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP