Clinical trial NCT04466345: Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder
Official title: Adjunctive Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder: a Randomized, Double-Blind, Placebo-Controlled Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Major Depressive Disorder
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2020-07-10
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Executive Function Composite Score
timeFrame: 16 Weeks
Secondary outcomes:
measure: Digit Symbol Substitution Test (DSST)
timeFrame: 16 Weeks
measure: Rey Auditory Verbal Learning Test (RAVLT)
timeFrame: 16 Weeks
measure: Stroop Test
timeFrame: 16 Weeks
measure: Trail Making Test A (TMTA)
timeFrame: 16 Weeks
measure: Perceived Deficits Questionnaire (PDQ)
timeFrame: 16 Weeks
measure: 36-Item Short Form Health Survey (SF-36)
timeFrame: 16 Weeks
measure: Sheehan Disability Scale (SDS)
timeFrame: 12 Weeks
measure: Endicott Workplace Productivity Scale (EWPS)
timeFrame: 16 Weeks
measure: Height
timeFrame: 16 Weeks
measure: Weight
timeFrame: 16 Weeks
measure: fasting glucose - Blood laboratorial marker
timeFrame: 16 Weeks
measure: Diet History Questionnaire III (DHQ)
timeFrame: 16 Weeks
measure: Physical Activity Questionnaire (IPAQ)
timeFrame: 16 Weeks
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 16 Weeks
measure: Trail Making Test B (TMTB)
timeFrame: 16 Weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Rodrigo B. Mansur, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: