Brain Insulin Resistance in Mood Disorders

NCT03915613 | Unknown Phase 1

• 1 other identifier: 17-5789.0
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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. 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. 2.Physiology: Measurement of peripheral sensitivity to insulin and metabolic correlates, including body mass index and dyslipidemia;
3. 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. 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).

Conditions

Major Depressive Disorder; Bipolar Disorder; Anhedonia; Intranasal Insulin

Outcome Measures

Primary Outcomes (1)

• Effort-Expenditure for Rewards Task (EEfRT)

  Score from the end of each treatment phase.

  2 weeks

Secondary Outcomes (12)

• Young Mania Rating Scale (YMRS)

  2 weeks

• Montgomery-Asberg Depression Scale (MADRS)

  2 weeks

• Snaith-Hamilton Pleasure Scale (SHAPS)

  2 weeks

• Perceived Deficits Questionnaire-Depression (PDQ-D)

  2 weeks

• Sheehan Disability Scale (SDS)

  2 weeks

Other Outcomes (9)

• Height (ft)

  2 weeks

• Weight (kg)

  2 weeks

• Blood Pressure (mmHG)

  2 weeks

Study Arms (2)

Insulin

EXPERIMENTAL

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

Drug: Humulin R

Sterile Diluent

PLACEBO COMPARATOR

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

Drug: Diluent

Interventions

Humulin R DRUG

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.

Insulin

Diluent DRUG

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.

Sterile Diluent

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60
• 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
• A written, voluntary informed consent prior to study enrollment

You may not qualify if:

• Use of insulin and/or oral hypoglycemiants, due to its confounding effects
• Diagnosis of possible or probable AD, MCI, or any other dementia
• History of neurological disorder, or evidence of neurologic or other physical illness that could produce cognitive deterioration
• Substance use disorder within 3 months before screening or a positive baseline toxicology screen
• Presence of clinically unstable general medical illness
• Pregnancy or breastfeeding
• MRI contraindications
• Age 18-60
• A written, voluntary informed consent prior to study enrollment
• Use of insulin and/or oral hypoglycemiants, due to its confounding effects
• Presence of any current or lifetime psychiatric or neurological conditions
• Substance use disorder within 3 months before screening or a positive baseline toxicology screen
• Presence of clinically unstable general medical illness
• Pregnancy or breastfeeding
• MRI contraindications

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, M5T2S8, Canada

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Bipolar Disorder; Anhedonia

Interventions

Insulin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Bipolar and Related Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Rodrigo B Mansur, M.D.

CONTACT

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

Joshua D Di Vincenzo, MSc.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist, Assistant Professor of Psychiatry at the University of Toronto

Model Details: Single-dose, randomized, double-blinded, cross-over study (150 participants) wherein study participants will receive a total of two doses (i.e., one insulin, one placebo) with a washout period of 1 week.

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: April 16, 2019
• Study Start: October 6, 2021
• Primary Completion: October 5, 2024
• Study Completion: October 5, 2024
• Last Updated: December 15, 2023

Record last verified: 2023-12

Locations

CA (1)