Major Depressive Disorder Clinical Trial
Official title:
A Randomized, Double-blind, Placebo-controlled Cross-over Trial Evaluating the Effect of Intranasal Insulin on Depressive Symptoms in Individuals With Major Depressive Disorder Insufficiently Responsive to Antidepressant Therapy
The primary aim of the study is to determine whether adjunctive intranasal insulin will exert an antidepressant effect when compared to placebo in adults with major depressive disorder (MDD), insufficiently responsive conventional antidepressants. There are three secondary aims of the study (1) to determine whether adjunctive intranasal insulin will alter emotional processing (i.e., cognitive-affective interface); (2) to determine whether early changes in emotional processing (i.e., after a single dose at 40IU intranasal insulin) predicts symptomatic improvement at study endpoint; and (3) to determine the effect of intranasal insulin on neurocognitive performance (e.g., learning and memory). This initiative represents a proof-of-concept study that insulin is important to depressive symptoms, neurocognitive functioning, and emotional processing deficits in MDD, representing a novel and safe therapeutic avenue.
Emerging evidence for impairments at the cognitive-affective interface, frequently defined
as affective cognition, are increasingly being recognized as a core feature of mood
disorders, particularly MDD. Individuals with MDD consistently exhibit abnormalities in
verbal memory with particular difficulty in memory tasks such as list learning and free
recall. The administration of intranasal insulin has been reported to improve verbal memory,
declarative memory in individuals with Alzheimer's disease or Mild Cognitive Impairment as
well as measures of mood (e.g., overall feeling of well-being, self-esteem, and depression)
in healthy volunteers. The effect of intranasal insulin on any measure of neurocognitive
function and emotional processing in MDD is currently unknown.
Thirty participants between the ages of 18 and 60 with DSM-IV-TR defined MDD [confirmed by
the Mini International Neuropsychiatric Interview (MINI)] will be enrolled. Individuals
below the age of 18 and over 60 are excluded as they are not seen at the recruiting center.
Enrollment into the study is voluntary. Eligible participants will provide written informed
consent. Participants will be enrolled from the outpatient Mood Disorders Psychopharmacology
Unit (MDPU), University Health Network (UHN), University of Toronto.
The MDPU case report form will gather information on the participant's course of illness
variables. Conventional pharmacological treatments for MDD will be permitted (e.g.,
conventional antidepressants). Conventional unimodal antidepressants modulate cerebral
glucose metabolism; as such, they will be kept consistent throughout the duration of the
study and will not be altered from the point of randomization to study endpoint.
Antidepressants and augmentation strategies with significant anti-cholinergic potential
(e.g., paroxetine, tricyclic antidepressants) as well as benzodiazepines will be
exclusionary as they may negatively affect neurocognitive function.
Participants will be excluded if they are receiving corticosteroids or antihypertensive
medications; misused substance or alcohol in the past 3 months; received electroconvulsive
therapy in the last 1 year; or have a neurological or medically unstable condition. Another
exclusion criterion includes the inability to provide written informed consent. The
Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale
17-Item (HAM-D-17) will be administered at baseline and weekly throughout the 8 weeks of
treatment assignment. Participants who are actively suicidal or evaluated as being a suicide
risk will also be excluded. Other reasons for discontinuation are impaired fasting glucose
(i.e., 6.1 - 6.9 mmol/L), and non-compliance (i.e., failure to administer ≥ 80% of the
assigned treatment in any week).
The ongoing provision of care is not contingent on enrollment and/or completion of the study
protocol. Furthermore, there will be ongoing communication with the participant's primary
care provider in regards to their participation in this study.
This is a randomized double-blind, placebo-controlled, cross-over study. The initial visit
entails the provision of detailed study information to the patient and obtainment of written
informed consent from the participant. The participant will then meet a research team member
at a later date for a screening visit. This study requires a total of 12 visits.
Full neuropsychological testing will be conducted at 4 time points:
1. Baseline1 (Visit 3)
2. Endpoint1 (Visit 7)
3. Baseline2 (Visit 8)
4. Endpoint2 (Visit 12)
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
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