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Effect of Intranasal Insulin on Depressive Symptoms in Major Depressive Disorder

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by University Health Network, Toronto
Sponsor:
Collaborator:
McMaster University
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00570050
First received: December 6, 2007
Last updated: February 20, 2014
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: Diluent / Insulin
Drug: Insulin / Diluent
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Montgomery-Asberg Depression Rating Scale [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    Score form baseline to end of each treatment phase.


Secondary Outcome Measures:
  • Affective Go/No-Go and Emotional Recognition Tasks; CGI Severity of Illness, Improvements in subjective mood (PANAS) and quality of life (Q-LES-Q) [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: June 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intranasal Insulin nasal spray Drug: Diluent / Insulin
Diluent (4 Weeks ) / Intranasal insulin (4 weeks)
Drug: Insulin / Diluent
Intranasal Insulin (4 Weeks ) / Diluent (4 Weeks)
Experimental: Placebo nasal spray (i.e., no active treatment) Drug: Diluent / Insulin
Diluent (4 Weeks ) / Intranasal insulin (4 weeks)
Drug: Insulin / Diluent
Intranasal Insulin (4 Weeks ) / Diluent (4 Weeks)

Detailed Description:

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)
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Major Depressive Disorder - current depression

Exclusion Criteria:

  • Unstable medical conditions
  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: NCT00570050

Contacts
Contact: Danielle S Cha 416-603-5800 ext 2024 danielle.cha@uhn.ca
Contact: Hanna O Woldeyohannes 416-603-5133 hanna.woldeyohannes@uhn.ca

Locations
Canada, Ontario
Toronto Western Hospital Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Danielle S Cha    416-603-5800 ext 2024    danielle.cha@uhn.ca   
Contact: Hanna O Woldeyohannes    416-603-5133    hanna.woldeyohannes@uhn.ca   
Sponsors and Collaborators
University Health Network, Toronto
McMaster University
Investigators
Principal Investigator: Roger S McIntyre University Health Network, Toronto
  More Information

Additional Information:
No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00570050     History of Changes
Other Study ID Numbers: Insulin-MDD
Study First Received: December 6, 2007
Last Updated: February 20, 2014
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Major Depressive Disorder, Memory, Executive function

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Disease
Behavioral Symptoms
Mental Disorders
Mood Disorders
Pathologic Processes
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 23, 2014