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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether brain insulin resistance links to depression in teens. Researchers will use MRI scans to examine how insulin, a hormone that helps control blood sugar, affects the brains of adolescents with depression. Participants will receive either an intranasal insulin spray (Humalog) or a placebo to determine insulin's effect on their condition. Teens aged 14 to 18 with a confirmed depression diagnosis or symptoms of depression, and without other complicating health issues, might be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on adolescent depression and insulin resistance.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have widely used Humalog to treat diabetes, providing some safety information. Humalog, a type of insulin, helps control blood sugar levels and is generally well-tolerated by people with diabetes.

This trial examines how Humalog might affect depression. Researchers aim to determine if insulin can influence the brain in a way related to depression. No direct evidence of safety issues exists for using Humalog in this context yet.

Since the FDA has approved Humalog for diabetes, it suggests safety when used correctly. However, safety information for using Humalog for depression is still being gathered. Prospective participants should consult a healthcare provider about the possible risks and benefits before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Humalog for treating depression in adolescents because it introduces a novel approach by using insulin, which is traditionally associated with diabetes management. Unlike standard treatments for depression, such as SSRIs or therapy, Humalog is delivered intranasally, offering a non-invasive and potentially quicker method of administration. This unique delivery targets brain pathways directly, which might offer rapid relief from depressive symptoms, setting it apart from existing options that often take weeks to show effects.

What evidence suggests that insulin therapy might be an effective treatment for depression in adolescents?

This trial will compare the effects of intranasal insulin (Humalog) with a placebo (saline nasal spray) in adolescents with depression. Research has not directly proven that Humalog, a type of insulin, can treat depression in teenagers. However, scientists are interested in insulin's role because depression and insulin resistance, particularly in people with diabetes, are linked. Some studies suggest that insulin might affect brain function and influence mood. Researchers are curious if improving the brain's use of insulin could help alleviate depression symptoms. Although this idea is still under investigation, understanding insulin's role in the brain might lead to new treatments for depression. ^{2 3 4 6 7}

Who Is on the Research Team?

Mahavir Agarwal, MD, PhD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

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

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. withpower.com withpower.com/trial/phase-insulin-resistance-8-2021-ae9f7

Insulin Therapy for Depression in Adolescents What data supports the effectiveness of the drug Humalog for treating depression in adolescents? There is no direct evidence supporting the use of Humalog ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4969210/

A randomized clinical trial aimed at preventing poor ... This study was designed to compare the effectiveness of a depression-prevention, resilience promotion program with an advanced diabetes education program.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03263351

Depression & Insulin Sensitivity in Adolescents In preliminary data, the investigators found initial evidence that a 6-week cognitive-behavioral group decreased depressive symptoms and prevented worsening of ...

4. nature.com nature.com/articles/s41398-025-03234-5

The interface of depression and diabetes: treatment ... This state-of-the-art review explores the relationship between depression and diabetes, highlighting the two-way influences that make treatment challenging.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11192657/

The psychosocial outcomes of advanced hybrid closed ... A recent review by Silina showed that adolescents with T1D and their parents were more predisposed to anxiety and depression symptoms than healthy somatic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12399406/

Impact of GLP‐1 Receptor Agonists on Suicide Behavior This meta‐analysis found no significant increase in suicidal behavior risk with GLP‐1 RAs versus controls. Results were consistent across ...

7. nature.com nature.com/articles/s41598-024-75965-2

The risk of depression, anxiety, and suicidal behavior in ... This study showed a significant association between GLP-1 RA treatment and an 98% increased risk of any psychiatric disorders.