Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder

University Health Network, Toronto

Status and phase: Active, not recruiting; Phase 2

Conditions: Major Depressive Disorder

Treatments: Biological: Placebo; Biological: Semaglutide

Study type: Interventional

Funder types: Other

Identifiers

NCT04466345

19-6283

Details and patient eligibility

About

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

Full 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.

Enrollment: 72 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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72 participants in 2 patient groups, including a placebo group

Semaglutide

Experimental group

Description:

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).

Treatment:

Biological: Semaglutide

Placebo

Placebo Comparator group

Description:

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

Treatment:

Biological: Placebo