Cognitive Dysfunction and Glucagon-like Peptide-1 Agonists

Sponsor
University Health Network, Toronto
Study ID
NCT02423824
Phase
PHASE3
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 45 Years
Healthy Volunteers
Not accepted

Interventions

  • Liraglutide — BIOLOGICAL
    Study participants will received the following study intervention in addition to 'standard of care' treatment: Adjunctive liraglutide will be initiated at 0.6 mg for the first 1 week, then increased to 1.2 mg with the option of increasing to 1.8 mg thereafter based on efficacy/tolerability (n=15 in each group). Liraglutide will be adjunctively administered to a conventional antidepressant, antipsychotic and mood stabilizing agent at guideline-concordant therapeutic plasma levels. Subjects will be randomized to receive liraglutide for a 4 week period. No major change in the pharmacological regimen will be permitted during the 4 week trial unless required for medical reasons.

Study Details

Cognitive deficits are a core feature across disparate brain disorders, being highly prevalent and pervasive. Impairments in executive function are one of the most consistent findings in clinical and meta-analytical studies and were reported to be a principal mediator of psychosocial impairment and disability. Cognitive dysfunction is thought to be underlied by abnormalities in distributed brain circuits, at the cellular and molecular levels. Nonetheless, the neural mechanisms underlying the dysregulation in these circuits are poorly understood. Emerging evidence indicates that metabolic abnormalities are highly relevant for the domain of cognitive function and indicate that alterations in metabolic pathways may be relevant to neurocognitive decline across different populations. The incretin glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal epithelial cells. GLP-1 receptors are widely expressed in the central nervous systems. Pre-clinical trials have demonstrated significant neuroprotective effects of GLP-1. Ongoing clinical trials measuring cognition and mood in populations with various psychiatric disorders lend further impetus to explore the effects of GLP-1R agonists on brain structure and cognitive function. We hypothesize that GLP-1 and the GLP-1R are relevant for molecular and cellular processes that are thought to underlie the formation and maintenance of brain circuits. A derivative of this hypothesis is that the administration of GLP-1 agonists may result in enhanced neuronal survival and consequential increase in gray matter volume. We therefore propose to explore the cellular and molecular abnormalities within and between neural circuits subserving cognition using the GLP-1R agonist liraglutide. The overall goal of this study is to explore the relationship between a metabolic molecular target (i.e. the GLP1 system), the neural circuits of interest and the behavioral phenotype cognitive function.

Key Dates

Start date
May 31, 2015
Status verified
May 2016
Primary completion
Apr 30, 2016
Completion
May 31, 2016

Study Design

Enrollment
21 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Active Comparator: Insulin Resistance
    Adjunctive Liraglutide 1.2-1.8mg/day
  • Active Comparator: Non-Insulin Resistance
    Adjunctive Liraglutide 1.2-1.8mg/day

Primary Outcome Measure

Executive function [ Time Frame: 4 weeks ]

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