Clinical Trials Logo

Clinical Trial Summary

This study will examine if brain insulin resistance is a feature of depression in humans using magnetic resonance imaging (MRI) measures sensitive to brain insulin action. This study will examine adolescents, as depression onset commonly occurs during this age, and the impacts of cumulative medication exposure and other lifestyle-related confounds are also lower in this age group, improving our ability to understand the underlying biology.


Clinical Trial Description

BACKGROUND: Major depressive disorder (MDD) is associated with metabolic dysfunction, including higher body mass index and increased risk for type 2 diabetes (T2D). This relationship is bidirectional as insulin resistance is associated with greater depressive symptom severity and worse cognition. These nested relationships between metabolic and mental health have encouraged a reconceptualization of MDD as a metabolic disorder. In this context, insulin in the brain has been implicated as a potential mediator unifying the mechanisms underlying metabolic and mental health. There is early evidence supporting this hypothesis; mice with brain-specific knockout of insulin receptor exhibited depression-like behavior that was reversed by treatment with monoamine oxidase inhibitors, while anti-diabetic agents that can potentially cross the blood-brain barrier have shown initial promise in reducing depressive symptoms. HYPOTHESES: 1) Adolescents diagnosed with MDD will have greater brain insulin resistance in comparison to matched healthy controls. 2) Greater brain insulin resistance will be associated with increased illness severity, worse cognitive performance, and worse short-term outcomes (i.e., at 6 months) in the depression group. 3) Greater peripheral insulin resistance (measured using fasting blood work) and hepatic and visceral adiposity (measured using MRI) will be associated with greater brain insulin resistance. APPROACH AND METHODOLOGY: Twelve adolescents with depression (14 to 18 years old) and 12 age-, sex-, and BMI-matched healthy controls will be recruited for the study. In a single-blinded crossover design, all 24 participants will undergo fasting blood work (glucose, insulin, and c-peptide) followed by an MRI-based protocol of brain insulin action. This includes two MRI scans; one with intranasal insulin challenge (80 IU) and one with intranasal placebo. This protocol leverages the property of intranasal insulin to induce resting state connectivity and blood flow changes in the brain. This will be achieved using a 3 Tesla (3T) MRI scanner, where participants will undergo a high-resolution T1-weighted structural scan, a resting state functional MRI scan, and an arterial spin labeling scan. Single voxel 1H-magnetic resonance spectroscopy will also be employed to examine changes in glutamate levels in the frontal and temporal cortex. The difference in change induced by intranasal insulin compared to that with intranasal placebo will be utilized as an index of insulin activity since any difference observed between placebo and insulin during this controlled manipulation is likely to be due to the intranasal insulin. THINC-it, a brief cognitive assessment, will also be performed to measure cognitive function in relation to insulin induced brain changes. An abdominal surface coil scan will also be used to measure visceral and hepatic adiposity. Participants with depression will be invited for a six-month follow-up visit to repeat fasting blood work, along with clinical and cognitive assessments. Age, sex, and BMI will be used as covariates in all analyses. SIGNIFICANCE: Demonstrating disrupted brain insulin action can provide novel insights into poorly understood mechanisms underlying the relationship between MDD and T2D. Evidence of brain insulin resistance early in the course of illness may also identify a modifiable risk factor that can be targeted using brain insulin sensitizers at the earliest stages of the illness. Thus, this work that lies at the intersection of psychiatry, physiology, and psychopharmacology has the potential to generate new knowledge and improve outcomes in an area of significant unmet need. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05571878
Study type Interventional
Source Centre for Addiction and Mental Health
Contact Mahavir Agarwal, MD, PhD
Phone 4165358501
Email mahavir.agarwal@camh.ca
Status Recruiting
Phase N/A
Start date September 1, 2021
Completion date December 1, 2024

See also
  Status Clinical Trial Phase
Active, not recruiting NCT05777044 - The Effect of Hatha Yoga on Mental Health N/A
Recruiting NCT04977232 - Adjunctive Game Intervention for Anhedonia in MDD Patients N/A
Recruiting NCT04680611 - Severe Asthma, MepolizumaB and Affect: SAMBA Study
Recruiting NCT04043052 - Mobile Technologies and Post-stroke Depression N/A
Completed NCT04512768 - Treating Comorbid Insomnia in Transdiagnostic Internet-Delivered Cognitive Behaviour Therapy N/A
Recruiting NCT03207828 - Testing Interventions for Patients With Fibromyalgia and Depression N/A
Completed NCT04617015 - Defining and Treating Depression-related Asthma Early Phase 1
Recruiting NCT06011681 - The Rapid Diagnosis of MCI and Depression in Patients Ages 60 and Over
Completed NCT04476446 - An Expanded Access Protocol for Esketamine Treatment in Participants With Treatment Resistant Depression (TRD) Who do Not Have Other Treatment Alternatives Phase 3
Recruiting NCT02783430 - Evaluation of the Initial Prescription of Ketamine and Milnacipran in Depression in Patients With a Progressive Disease Phase 2/Phase 3
Recruiting NCT05563805 - Exploring Virtual Reality Adventure Training Exergaming N/A
Completed NCT04598165 - Mobile WACh NEO: Mobile Solutions for Neonatal Health and Maternal Support N/A
Completed NCT03457714 - Guided Internet Delivered Cognitive-Behaviour Therapy for Persons With Spinal Cord Injury: A Feasibility Trial
Recruiting NCT05956912 - Implementing Group Metacognitive Therapy in Cardiac Rehabilitation Services (PATHWAY-Beacons)
Completed NCT05588622 - Meru Health Program for Cancer Patients With Depression and Anxiety N/A
Recruiting NCT05234476 - Behavioral Activation Plus Savoring for University Students N/A
Active, not recruiting NCT05006976 - A Naturalistic Trial of Nudging Clinicians in the Norwegian Sickness Absence Clinic. The NSAC Nudge Study N/A
Enrolling by invitation NCT03276585 - Night in Japan Home Sleep Monitoring Study
Terminated NCT03275571 - HIV, Computerized Depression Therapy & Cognition N/A
Completed NCT03167372 - Pilot Comparison of N-of-1 Trials of Light Therapy N/A