Investigating insulin's role in mood disorders

Brain Insulin Resistance and Motivation in Mood Disorders

This study is testing how insulin might affect mood and feelings of pleasure in adults with major depression or bipolar disorder compared to healthy individuals.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: University Health Network, Toronto (Academic / other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT03915613 on ClinicalTrials.gov

What this trial studies

This study aims to explore how insulin signaling affects the neurobiological mechanisms related to anhedonia in individuals with Major Depressive Disorder (MDD) and Bipolar Disorder (BD). It will involve 75 adults aged 18 to 50 with these mood disorders, alongside 75 healthy controls, to assess molecular, physiological, and neural circuit responses to intranasal insulin. Participants will undergo evaluations using proteomics, gene expression, and functional MRI to understand insulin's impact on reward-related behaviors. The study is randomized, double-blind, and placebo-controlled, ensuring rigorous methodology.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 50 with a diagnosis of MDD or BD experiencing a depressive episode.

Not a fit: Patients with a history of neurological disorders, dementia, or those currently using insulin or oral hypoglycemics may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new therapeutic strategies targeting insulin signaling to improve mood disorder treatments.

How similar studies have performed: While the specific approach of using intranasal insulin in mood disorders is novel, related studies have shown potential benefits of insulin in metabolic and neuropsychiatric conditions.

Eligibility criteria

Inclusion criteria (patients):

1. Age 18-60
2. DSM-5 defined MDD/BD and a total score ≥20 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and no history of dementia or intellectual disability
3. A written, voluntary informed consent prior to study enrollment

Exclusion criteria (patients):

1. Use of insulin and/or oral hypoglycemiants, due to its confounding effects
2. Diagnosis of possible or probable AD, MCI, or any other dementia
3. History of neurological disorder, or evidence of neurologic or other physical illness that could produce cognitive deterioration
4. Substance use disorder within 3 months before screening or a positive baseline toxicology screen
5. Presence of clinically unstable general medical illness
6. Pregnancy or breastfeeding
7. MRI contraindications

Inclusion criteria (healthy controls):

1. Age 18-60
2. A written, voluntary informed consent prior to study enrollment

Exclusion criteria (healthy controls):

1. Use of insulin and/or oral hypoglycemiants, due to its confounding effects
2. Presence of any current or lifetime psychiatric or neurological conditions
3. Substance use disorder within 3 months before screening or a positive baseline toxicology screen
4. Presence of clinically unstable general medical illness
5. Pregnancy or breastfeeding
6. MRI contraindications

Where this trial is running

Toronto, Ontario

• Toronto Western Hospital — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Rodrigo B Mansur, M.D.

Conditions Major Depressive Disorder; Bipolar Disorder; Anhedonia; Intranasal Insulin