Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04466345
• Other study ID #: 19-6283
• Status: Recruiting
• Phase: Phase 2
• Start date: October 6, 2021
• Est. completion date: October 5, 2024

Study information

• Verified date: May 2023
• Source: University Health Network, Toronto
• Contact: Rodrigo B. Mansur, MD, PhD
• Phone: 416 603 5106
• Email: rodrigo.mansur[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 5, 2024
• Est. primary completion date: October 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

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
Semaglutide placebo capsules

Locations

Country	Name	City	State
Canada	Toronto Western Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

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