Recruiting
Phase 2

Clemastine

Sponsor:

University of Illinois at Chicago

Code:

NCT06591091

Conditions

Depression

Eligibility Criteria

Sex: All

Age: 60+

Healthy Volunteers: Not accepted

Interventions

Clemastine Fumarate

Placebo

Study Details

Brief summary:

The goal of this study is to find out if the antihistamine, clemastine, can make the white matter in the brain better in older adults with depression. The study will also determine whether this improvement can make antidepressant treatment work better, reduce depressive symptoms, and improve memory and thinking.

Conditions

Depression

Study ID

NCT06591091

Start date

Dec 10, 2025

Status verified date

Aug, 2025

Completion date

Dec, 2026

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 60+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age > 60 years
  • Diagnosis of major depressive disorder, single or recurrent episode (DSM5)
  • Symptom Severity: MADRS ≥ 15
  • Seeking antidepressant treatment
  • Cognition score of MoCA >24
  • Fluent in English or Spanish

Exclusion Criteria:

  • Other Axis I psychiatric disorders, except for simple phobia or anxiety disorders present uniquely during the depressive episode (e.g., generalized anxiety disorder (GAD) or panic disorder symptoms)
  • History of alcohol or drug dependence or abuse in the last year
  • History of a developmental disorder or history of IQ (intelligence quotient) <70
  • Acute suicidality ideation within the past month as determined by the Columbia Suicide Severity Rating Scale (C-SSRS)
  • Acute grief (<1 month)
  • Current or past psychosis
  • Primary neurological disorder, including dementia, clinical stroke, brain tumor, epilepsy, etc.
  • Presence of unstable medical illness requiring urgent treatment
  • Any MRI contraindication
  • Electroconvulsive Therapy (ECT) in last 6 months

Study Design

Enrollment

80 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Clemastine arm

Participants in the clemastine arm of the study will receive clemastine 5.36 mg PO twice daily for 12 weeks. Based on clinical assessment, participants will also receive one of the following antidepressant medications: SSRI: Fluoxetine, sertraline, citalopram, escitalopram, vilazodone, vortioxetine SNRI: Venlafaxine, desvenlafaxine, duloxetine, levomilnacipran Augmentation: Bupropion and mirtazapine (monotherapy option in addition to first augmentation level), aripiprazole and quetiapine (second augmentation level).

Allowable concomitant medications parallel clinical practice. These can include trazodone (up to 100mg nightly) for insomnia or as-needed use of benzodiazepines for concomitant anxiety, up to a maximum daily dose equivalent to lorazepam 2mg daily. Psychotropic medications used for other indications (such as tricyclics or gabapentin for pain) are allowable. Concomitant psychotherapy is allowed.

placebo comparator: Placebo arm

Participants in the placebo arm of the study will receive a placebo capsule PO twice daily for 12 weeks.

Interventions

Clemastine Fumarate

Listed in arm/group description

Placebo

Listed in arm/group description

Primary outcome measure

  • Frequency, Intensity and Burden of Side Effects Rating Scale [ Time Frame: 12 weeks ]
  • Montgomery-Asberg Rating Scale for Depression [ Time Frame: 12 weeks ]
  • Quantitative Anisotropy [ Time Frame: 12 weeks ]
  • Fractional Anisotropy [ Time Frame: 12 weeks ]

Central Contacts and Locations

Central contacts

Olu A Ajilore, MD, PhD

312-413-4562oajilore@uic.edu

Locations

University of Illinois College of Medicine

Recruiting

Chicago, Illinois, United States, 60612

Contacts

Olusola Ajilore, MD, PhD

312-413-4562oajilore@uic.edu

More Information

Sponsor

University of Illinois at Chicago

Last update posted

Jun 30, 2026

Last verified

Aug, 2025

Keywords

  • Late-life Depression
  • Antidepressant medication response

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Illinois at Chicago on 2026-06-30.