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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: May 4, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Impaired Glucose Tolerance Associated With Drugs
Drug: Liraglutide
Drug: Liraglutide Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Does a GLP-1 Receptor Agonist Change Glucose Tolerance in Antipsychotic-treated Patients? A Randomized, Double-blinded, Placebo-controlled Clinical Trial

Resource links provided by NLM:


Further study details as provided by Psychiatric Centre Rigshospitalet:

Primary Outcome Measures:
  • 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))


Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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.


Enrollment: 103
Study Start Date: April 2013
Estimated Study Completion Date: March 2017
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Liraglutide
Once a day 1,8 mg subcutaneous injection for 16 weeks
Drug: Liraglutide
Once a day 1,8 mg subcutaneous injection for 16 weeks
Other Names:
  • Victoza
  • GLP-1 agonist
Placebo Comparator: Liraglutide placebo
Once a day 1,8 mg subcutaneous injection for 16 weeks
Drug: Liraglutide Placebo
Once a day 1,8 mg subcutaneous injection for 16 weeks
Other Name: Placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01845259

Locations
Denmark
Psychiatric Centre Rigshospitalet
Copenhagen, København Ø, Denmark, 2100
Sponsors and Collaborators
Psychiatric Centre Rigshospitalet
University Hospital, Gentofte, Copenhagen
University of Cambridge
Investigators
Principal Investigator: Anders Fink-Jensen, MD, DMSci Psychiatric Centre Rigshospitalet
Principal Investigator: Tina Vilsbøll, MD, DMSci Diabetes Research Division, Gentofte
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Anders Fink-Jensen, MD, DMSci, Professor, MD, DMSci, Psychiatric Centre Rigshospitalet
ClinicalTrials.gov Identifier: NCT01845259     History of Changes
Other Study ID Numbers: GLP-1 antipsychotics  2013-000121-31  U1111-1128-3404 
Study First Received: April 14, 2013
Last Updated: May 4, 2016
Health Authority: Denmark: Danish Health and Medicines Authority

Additional relevant MeSH terms:
Glucose Intolerance
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Liraglutide
Antipsychotic Agents
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs

ClinicalTrials.gov processed this record on December 08, 2016