Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder

Adjunctive Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder: a Randomized, Double-Blind, Placebo-Controlled Study

This study will examine whether semaglutide may improve cognitive function in individuals with major depressive disorder (MDD).

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Biological: Semaglutide; Biological: Placebo

Detailed Description

This is a 16-week, placebo-controlled, randomized, double-blind, clinical trial, involving 60 overweight individuals with MDD and pre-treatment cognitive dysfunction. Study participants will receive one of the following study interventions in addition to 'standard of care' treatment: once-daily semaglutide, initiated at 3 mg/day for 4 weeks, increased to 7 mg/day for 4 more weeks and titrated to 14 mg/day for the subsequent 8 weeks; or matching placebo. Participants will be assessed to examine the effect of semaglutide on their cognitive function.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rodrigo B. Mansur, MD, PhD; Phone Number: 416 603 5106; Email: rodrigo.mansur@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Recruiting
      • Toronto Western Hospital
      • Contact: Joshua Di Vincenzo; Email: joshua.divincenzo@uhnresearch.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Informed consent before study-related activity
2. Individuals between the ages of 18 and 60 who meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for MDD
3. Overweight (i.e. BMI ≥ 25 kg/m2)
4. Below-average (i.e. >1 SD below norm) performance in the Trail Making Test-B (TMTB)

Exclusion Criteria:

1. Current, or in the past 4 weeks, treatment with other oral hypoglycemic agents and/or insulin
2. Diagnosis of possible or probable Alzheimer's Disease, Mild Cognitive Impairment, or any other dementia
3. History of neurological disorder, or evidence of neurologic or other physical illness that could produce cognitive deterioration
4. Severe mood episode, defined as a Hamilton Depression Rating Scale (HAMD-17) score of >23
5. Actively suicidal or evaluated as being a suicide risk (operationalized as a score of ≥3 on HAMD-17 suicide item and/or by clinical assessment).
6. Substance use disorder within 3 months before screening or a positive baseline toxicology screen
7. DSM-5 diagnosis of obsessive compulsive disorder, posttraumatic stress disorder (current or within the last year), or borderline personality disorder as assessed by a study investigator
8. Presence of absolute or relative contraindication to semaglutide (e.g. hypersensitivity to semaglutide, hepatic impairment, renal impairment with chronic kidney disease stage 3 and above, personal or familial history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2)
9. History of diabetic retinopathy
10. History of pancreatitis or pancreatic cancer
11. Presence of clinically unstable general medical illness
12. Pregnancy or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide; Participants receive semaglutide once daily orally, initiated at 3 mg/day for 4 weeks, increased to 7 mg/day for 4 more weeks and titrated to 14 mg/day for the subsequent 8 weeks (i.e., duration of 16 weeks in total).	Biological: Semaglutide; 3 mg/day for 4 weeks, increased to 7 mg/day for 4 more weeks and titrated to 14 mg/day for the subsequent 8 weeks
Placebo Comparator: Placebo; Participants receive matching semaglutide placebo capsules once daily (duration of 16 weeks).	Biological: Placebo; Semaglutide placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Executive Function Composite Score	The primary outcome will be an executive function composite score. This score will be comprised of the Digit Symbol Substitution Test (DSST - number of symbols), the Stroop test (time to completion in the congruent and incongruent conditions), and the Spatial n-back (reaction times and accuracy in four conditions,1-back, 2-back, 3-back, and 4-back).	16 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sheehan Disability Scale (SDS)	SDS is used to assess functional impairment in work/school, social life, and family life.	12 Weeks
Digit Symbol Substitution Test (DSST)	DSST is a neurocognitive test designed to assess motor speed and concentration.	16 Weeks
Rey Auditory Verbal Learning Test (RAVLT)	RAVLT is a neurocognitive test designed to assess verbal learning and memory.	16 Weeks
Stroop Test	The Stroop Test is a neurocognitive test designed to assess the ability to inhibit cognitive interference.	16 Weeks
Trail Making Test A (TMTA)	TMTA is a neurocognitive test designed to assess visual scanning and attention.	16 Weeks
Perceived Deficits Questionnaire (PDQ)	PDQ is used to assess subjective cognitive dysfunction.	16 Weeks
36-Item Short Form Health Survey (SF-36)	SF-36 is used to assess quality of life.	16 Weeks
Endicott Workplace Productivity Scale (EWPS)	EWPS is used to assess workplace productivity.	16 Weeks
Height	Unit: cm	16 Weeks
Weight	Unit: kg	16 Weeks
fasting glucose - Blood laboratorial marker		16 Weeks
Diet History Questionnaire III (DHQ)	DHQ is a freely available questionnaire used to assess dietary intake (https://epi.grants.cancer.gov/dhq3/).	16 Weeks
Physical Activity Questionnaire (IPAQ)	IPAQ is used to assess physical activity.	16 Weeks
Pittsburgh Sleep Quality Index (PSQI)	PSQI is used to assess sleep quality.	16 Weeks
Trail Making Test B (TMTB)	TMTB is a neurocognitive test designed to assess attention and concentration.	16 Weeks

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Rodrigo B. Mansur, MD, PhD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2021
• Primary Completion (Estimated): October 5, 2024
• Study Completion (Estimated): October 5, 2024

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: July 9, 2020
• First Posted (Actual): July 10, 2020

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Neurocognitive Disorders; Cognition Disorders; Depression; Depressive Disorder; Cognitive Dysfunction; Depressive Disorder, Major
• Other Study ID Numbers: 19-6283

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes