Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder

NCT04466345 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 19-6283
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Digit Symbol Substitution Test (DSST)

  16 Weeks

• Rey Auditory Verbal Learning Test (RAVLT)

  16 Weeks

• Stroop Test

  16 Weeks

• Trail Making Test A (TMTA)

  16 Weeks

• Perceived Deficits Questionnaire (PDQ)

  16 Weeks

Study Arms (2)

Semaglutide

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Participants receive matching semaglutide placebo capsules once daily (duration of 16 weeks).

Biological: Placebo

Interventions

Semaglutide BIOLOGICAL

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

Semaglutide

Placebo BIOLOGICAL

Semaglutide placebo capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Current, or in the past 4 weeks, treatment with other oral hypoglycemic agents and/or insulin
• Diagnosis of possible or probable Alzheimer's Disease, Mild Cognitive Impairment, or any other dementia
• History of neurological disorder, or evidence of neurologic or other physical illness that could produce cognitive deterioration
• Severe mood episode, defined as a Hamilton Depression Rating Scale (HAMD-17) score of \>23
• 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).
• Substance use disorder within 3 months before screening or a positive baseline toxicology screen
• 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
• 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)
• History of diabetic retinopathy
• History of pancreatitis or pancreatic cancer
• Presence of clinically unstable general medical illness
• Pregnancy or breastfeeding women

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Rodrigo B. Mansur, MD, PhD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: July 10, 2020
• Study Start: October 6, 2021
• Primary Completion: December 27, 2024
• Study Completion: December 27, 2024
• Last Updated: October 2, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)