Brain Insulin Resistance and Motivation in Mood Disorders

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 60
Healthy Volunteers: t
View:

• 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

• Age 18-60

• A written, voluntary informed consent prior to study enrollment

Locations
Other Locations
Canada
Toronto Western Hospital
RECRUITING
Toronto
Contact Information
Primary
Rodrigo B Mansur, M.D.
Rodrigo.mansur@uhn.ca
(416) 603-5800
Backup
Joshua D Di Vincenzo, MSc.
joshua.divincenzo@uhnresearch.ca
416-603-5800
Time Frame
Start Date: 2021-10-06
Estimated Completion Date: 2024-10-05
Participants
Target number of participants: 150
Treatments
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
Related Therapeutic Areas
Sponsors
Leads: University Health Network, Toronto

This content was sourced from clinicaltrials.gov