Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder

Phase 2

Active, not recruiting

• Conditions: Major Depressive Disorder
• Interventions: Biological: Placebo; Biological: Semaglutide

• Registration Number: NCT04466345
• Lead Sponsor: University Health Network, Toronto

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-06-08
• Study First Submitted QC: 2020-07-09
• Study First Posted: 2020-07-10
• Study Start: 2021-10-06
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-12
• Last Update Posted: 2024-08-13
• Primary Completion: 2024-10-05
• Study Completion: 2024-10-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 72

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants receive matching semaglutide placebo capsules once daily (duration of 16 weeks).
Semaglutide	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).

Primary Outcome Measures

Name	Time	Method
Executive Function Composite Score	16 Weeks	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).

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Toronto Western Hospital; 🇨🇦 Toronto, Ontario, Canada