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Region Hovedstaden - en del af Københavns Universitetshospital

THE TAO STUDY - TREATMENT OF ANTIPSYCHOTIC - ASSOCIATED OBESITY WITH A GLP-1-ANALOGUE

Projekt: Typer af projekterProjekt

  1. No cognitive-enhancing effect of GLP-1 receptor agonism in antipsychotic-treated, obese patients with schizophrenia

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Boehringer-Ingelheim CONNEX 3

    Projekt: Typer af projekterProjekt

  2. PRESCIENT

    Projekt: Typer af projekterProjekt

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Aims
To examine the effects of 3 months treatment with a GLP-1 analogue can reduce antipsychotic-associated obesity in non-diabetic patients with a diagnosis within the schizophrenic spectrum. Moreover, we will investigate associations between GLP-1 analogue treatment and peripheral metabolic parameters, as well as associations with central physiological parameters such as functional magnetic resonance imaging (fMRI) scans of the brain and cognitive tests.
The background and the framework for the TAO study has recently been published (Ebdrup et al. BMC Medicine 2012)

Study design
Randomized, placebo-controlled doubleblinded trial.

Number of patients
Minimum 20 patients in each arm will be included at baseline. Enrollment will continue until 20 patients have been through each arm.

Inclusions criteria:
- Age: 18-65 years
- Diagnosis of the schizophrenia spectrum (ICD-10: F20.x, F25.x) both in-patients and out-patients will be included
- Current and unchanged treatment with at least one antipsychotic drug (FGA andR SGA and/or depot treatment)
- BMI > 30 kg/m2
- HbA1c < 6,5%

Exclusions criteria:
- Substance dependence (ICD-10: F1x.2 (apart from nicotine addiction F17.2)
- Diabetes or HbA1c > 6,5%
- Contraindications to MRI (Metal implants, pacemakers, severe claustrophobia, > 150 kg (max bed weight in th MRI scanner))
- Previous head trauma with a loss of consciousness for more than 5 minutes
- Pregnancy (screened by urin human chorionic gonadotropin (hCG), lactation or no acceptance to use effective contraception during the intervention period
- Severe somatic disease, including inflammatory bowel disease and chronic ketoacidosis
- Allergy to exenatide
- Coercive measures according to Danish Law of Psychiatry
- Conditions that according to sponsor are not congruous with participation in the study

Intervention
Patients will be randomized to subcutaneous (sc) exenatide 2 mg once weekly or sc placebo injection once weekly for 3 months (adjuvant to usual treatment) or treatment as ususal.

Endpoints
The primary endpoint is weight loss after 3 months of treatment with a GLP-1 analogue. Furthermore, the effect of GLP-1 analogue treatment on a wide range of secondary endpoints will be examined. Thus, as a unique feature of the present study, detailed physiological, cognitive and behavioural parameters will be intensively investigated: By means of MRI, potential neuroprotective effects and changes in cerebral blood flow will be explored. Observed brain changes will be related to potential improvements in cognitive performance, with particular focus on hippocampal volume changes and specific memory tests. Changes in cerebral blood flow following GLP-1 analogue treatment, with particular focus on the blood flow in hypothalamus and prefrontal cortex, will be correlated to measures of global cognitive ability. Moreover, associations between GLP-1 analogue treatment, weight loss and improvement in secondary metabolic parameters will be associated with improvements in the patients' subjective quality of life. Finally, we will examine if possible GLP-1 analogue-induced volumetric changes in the striatum are correlated with reductions in the extrapyramidal side effects of antipsychotic medication.

Study duration
Three years.
StatusAfsluttet
Periode28/05/201229/02/2016
FinansieringskildeAnden offentlig støtte (Offentlig)
ForskningsprogramKøbenhavns Universitet/Copenhagen Graduate School of Health Sciences
Beløb1.650.000,00 Danske Kroner
Årstal2012

ID: 36377203