Insulin Therapy for Depression in Adolescents

Overseen By Mahavir Agarwal, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Antipsychotics, Mood stabilizers

Disqualifiers: Substance use disorder, Diabetes, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

24 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you do not use antipsychotics, mood stabilizers, weight, lipids, or blood pressure reducing agents. If you are taking these medications, you would need to stop them to participate.

What data supports the effectiveness of the drug Humalog for treating depression in adolescents?

There is no direct evidence supporting the use of Humalog, an insulin, for treating depression in adolescents. However, managing diabetes effectively with insulin like Humalog can help improve overall health, which might indirectly support better mental health outcomes. ^{1 2 3 4 5}

How does the drug Humalog differ from other treatments for depression in adolescents?

Humalog, an insulin used primarily for diabetes, is unique in this trial for depression as it targets insulin regulation, which is not a standard approach for treating depression. This novel use explores the potential link between insulin levels and mood regulation, differing from typical antidepressants that focus on neurotransmitters like serotonin. ^{6 7 8 9 10}

Research Team

Mahavir Agarwal, MD, PhD

Principal Investigator

Centre for Addiction and Mental Health

Eligibility Criteria

Adolescents aged 14-18 with Major Depressive Disorder or Persistent Depressive Disorder, or those showing significant depressive symptoms. Participants must have a BMI within the 15th to 85th percentile and cannot have liver or kidney disease, allergies to insulin, MRI contraindications, positive pregnancy test, glucose tolerance issues, psychotic illness history, severe substance use disorder (except certain cases for cannabis and alcohol), nor be on specific medications affecting weight or blood pressure.

Inclusion Criteria

I am between 14 and 18 years old.

BMI between 5-95th population percentile and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≤2.5 calculated using fasting blood work values (glucose and insulin)

I have been diagnosed with MDD or PDD, or scored high for depression on a questionnaire.

Exclusion Criteria

I have pre-diabetes or diabetes.

History of current substance use disorder (moderate to severe)

Evidence of impaired glucose tolerance on screening oral glucose tolerance test (OGTT)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo fasting blood work and initial MRI scans to assess brain insulin resistance

1 week

1 visit (in-person)

Crossover Treatment

Participants receive intranasal insulin and placebo in a crossover design to measure brain insulin activity

2 weeks

2 visits (in-person)

Follow-up

Participants with depression are monitored for changes in brain insulin resistance and cognitive function

6 months

1 visit (in-person)

Treatment Details

Interventions

• Humalog
• Saline Nasal Spray

Trial Overview The trial is testing whether brain insulin resistance is associated with depression in adolescents. It involves using MRI scans sensitive to brain insulin action. The interventions include Humalog (a rapid-acting insulin) and saline nasal spray as a control comparison.

Participant Groups

Group I: Crossover: Insulin and Placebo Experimental Treatment 2 Interventions

Twelve adolescents who have a confirmed depression diagnosis or experiencing depression will be used as the study population group against 12 healthy adolescents who will be used as the healthy study population group. Both the health control group and medication-free adolescents with depression will receive the same drug conditions (intranasal insulin and intranasal placebo).

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

References

1. England pubmed.ncbi.nlm.nih.gov

Depression in adolescents with diabetes. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Depressive Symptoms in Youth With Type 1 or Type 2 Diabetes: Results of the Pediatric Diabetes Consortium Screening Assessment of Depression in Diabetes Study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Depression and diabetes: treatment and health-care delivery. [2017]

4. Denmark pubmed.ncbi.nlm.nih.gov

Depressive symptoms predict change in glycemic control in adolescents with type 1 diabetes: rates, magnitude, and moderators of change. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Glycemic control, depression, diabetes distress among adolescents with type 2 diabetes: effects of sex, race, insurance, and obesity. [2022]

6. Brazil pubmed.ncbi.nlm.nih.gov

New options in insulin therapy. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Patterns of insulin therapy and insulin daily doses in children and adolescents with type 1 diabetes in Germany. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Insulin therapy in children and adolescents. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of Children and Adolescents with Type 1 Diabetes Mellitus. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

[Current aspects in therapy of insulin-dependent diabetes mellitus in children and adolescents]. [2014]