Recruiting
Phase 1
Phase 2

Observational Study

Sponsor:

University Health Network, Toronto

Code:

NCT03915613

Conditions

Major Depressive Disorder

Bipolar Disorder

Anhedonia

Intranasal Insulin

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Accepted

Interventions

Humulin R

Diluent

Study Details

Brief summary:

The overarching aim of the study is to determine the role of insulin signaling on the neurobiological substrates subserving anhedonia within individuals with mood disorders (i.e., Bipolar Disorder (BD) and Major Depressive Disorder (MDD)).

Specific aims include:

1. Molecular: Assessment of components of the insulin cascade, as well as of anhedonia and reward-related processes, using a proteomics and gene expression approach;
2. Physiology: Measurement of peripheral sensitivity to insulin and metabolic correlates, including body mass index and dyslipidemia;
3. Neural Circuits: Evaluation of the insulin sensitivity of prefrontal (e.g. prefrontal cortex) and striatal (e.g. nucleus accumbens, ventral tegmental area) networks in the resting-state and during an effort-based decision making test, using acutely administered intranasal insulin and functional magnetic resonance imaging (fMRI);
4. Behavioral: Measurement of willingness to make effort for rewards, as well as of other components of reward response and anhedonia, using validated behavioral tasks and clinical scales (e.g. Snaith-Hamilton Pleasure Scale - SHPS).

This initiative represents a proof-of-concept study that insulin is important to anhedonia, neurocognitive functioning, and behavioural deficits in MDD, representing a novel and safe therapeutic avenue.

Conditions

Major Depressive Disorder

Bipolar Disorder

Anhedonia

Intranasal Insulin

Study ID

NCT03915613

Start date

Oct 6, 2021

Status verified date

Dec, 2023

Completion date

Oct 5, 2024

Anticipated

Primary completion date

Oct 5, 2024

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Accepted

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

Study Design

Enrollment

150 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Insulin

Intranasal insulin will be made prepared from Humulin® R \[insulin injection, human biosynthetic (rDNA Origin) REGULAR; 10 mL/vial, manufactured by Eli Lilly\]. Each mL contains: 100 units of insulin injection, human biosynthetic (rDNA Origin) REGULAR. Nonmedicinal ingredients contain: glycerol, hydrochloric acid, m-cresol, sodium hydroxide and water for injection.

Unopened vials should be stored under refrigeration between 2°C and 8°C (36°F to 46°F) until the expiration date; do not freeze; keep away from heat and sunlight. Once punctured (in use), Humulin vials should be stored at room temperature <25°C (<77°F) and discarded after 28 days.

To obtain a dose Humulin R 160 U / placebo

  • 16 sprays (0.1 mL/spray) are to be given per dose
  • This works out to 16 sprays split between each nostril such that each nostril receives 8 sprays.
  • The sprays will be administered between alternating nostrils

placebo comparator: Sterile Diluent

Intranasal placebo will be prepared from Eli Lilly's sterile diluent used with Humulin® R (10 mL/vial, manufactured by Eli Lilly). Nonmedicinal ingredients contain: dibasic sodium phosphate, glycerin, liquefied phenol, metacresol, hydrochloric acid, sodium hydroxide and water for injection.

Unused sterile diluent should be kept at controlled room temperature until the expiration date. The USP defines controlled room temperature as (20° to 25°C \[68° to 77°F\]), with excursions permitted (15° to 30°C \[59° to 86°F\]). Once in-use, the sterile diluent vial should be used within 28 days.

Participants will follow the same dosage, frequency, and administration as Humulin:

  • 16 sprays (0.1 mL/spray) are to be given per dose
  • This works out to 16 sprays split between each nostril such that each nostril receives 8 sprays.
  • The sprays will be administered between alternating nostrils

Interventions

Humulin R

The investigator and/or designee will instruct the study participant on how the intranasal insulin spray should be administered. Each study participant is to receive a single dose of Humulin R 160 U.

The nasal spray bottles provide a deliverable volume of 0.1 mL/spray. Humulin R insulin will be sourced as 100 units/mL in a vials of 10 mL from Eli Lilly. 16 sprays in alternating nostrils (8 per nostril) will be administered per dose.

Diluent

The investigator and/or designee will instruct the study participant on how the intranasal placebo spray should be administered. Each study participant is to receive a single dose of placebo.

The nasal spray bottles provide a deliverable volume of 0.1 mL/spray. Diluent will be sourced as 10 mL/vial from Eli Lilly. 16 sprays in alternating nostrils (8 per nostril) will be administered per dose.

Primary outcome measure

  • Effort-Expenditure for Rewards Task (EEfRT) [ Time Frame: 2 weeks ]

Central Contacts and Locations

Central contacts

Rodrigo B Mansur, M.D.

(416) 603-5800Rodrigo.mansur@uhn.ca

Joshua D Di Vincenzo, MSc.

416-603-5800joshua.divincenzo@uhnresearch.ca

Locations

Toronto Western Hospital

Recruiting

Toronto, Ontario, Canada, M5T2S8

Contacts

Rodrigo B Mansur, M.D.

416-603-3125rodrigo.mansur@uhn.ca

Principal Investigator:

Rodrigo B Mansur, M.D.

More Information

Sponsor

University Health Network, Toronto

Last update posted

Dec 15, 2023

Last verified

Dec, 2023

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University Health Network, Toronto on 2023-12-15.