Clemastine for Improving White Matter and Boosting Antidepressant Response in Late-life Depression

Phase 2

Not yet recruiting

• Conditions: Depression
• Interventions: Drug: Clemastine Fumarate; Drug: Placebo

• Registration Number: NCT06591091
• Lead Sponsor: University of Illinois at Chicago

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.

Detailed Description

Geriatric depression, also known as late-life depression, is a type of major depression that affects people who are 60 years old or older. It can be difficult to treat and often comes back after treatment. It can also lead to problems with memory and thinking. Some studies have found that problems with the white matter in the brain can make it harder to treat depression in older adults. White matter helps with communication in the brain. A new study suggests that a medicine called clemastine might be able to improve the white matter in the brain. Clemastine is usually used as an antihistamine, but it might also help the brain repair itself. The goal of this study is to find out if 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. The study will involve two groups of participants. One group will receive the standard antidepressant treatment along with a placebo, while the other group will receive the standard antidepressant treatment along with clemastine. The investigators will compare the effects of these two treatments over a period of 12 weeks. The investigators will measure the improvement in white matter using special brain imaging techniques. The investigators will also assess the participants' mood, memory, and thinking abilities, and keep track of any side effects or problems caused by the treatments. Overall, this study has the potential to contribute valuable insights into the treatment of geriatric depression, alleviate depressive symptoms, enhance cognitive function, and potentially open up new avenues for future research and therapeutic approaches.

Study Timeline

• Study First Submitted: 2024-08-05
• Study First Submitted QC: 2024-09-06
• Study First Posted: 2024-09-19
• Status Verified: 2024-11
• Last Update Submitted: 2025-02-27
• Last Update Posted: 2025-03-04
• Study Start: 2025-04
• Primary Completion: 2026-03
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 80

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Clemastine arm	Clemastine Fumarate	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 arm	Placebo	Participants in the placebo arm of the study will receive a placebo capsule PO twice daily for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Frequency, Intensity and Burden of Side Effects Rating Scale	12 weeks	The investigator will examine the safety of clemastine using the Frequency, Intensity, and Burden of Side Effects Rating Scale (FIBSER).; The FIBSER is scored from 0-6, with higher scores indicating worse outcomes
Montgomery-Asberg Rating Scale for Depression	12 weeks	The investigators will examine the effectiveness of an antidepressant plus clemastine (5.36 mg twice daily) compared to antidepressant plus placebo on clinical outcomes as indexed by the Montgomery-Asberg Rating Scale for Depression (MADRS).; The MADRS is scored from 0-60, with higher scores indicating a worse outcome
Quantitative Anisotropy	12 weeks	The investigators will measure the impact of an antidepressant plus clemastine (5.36 mg twice daily) compared to antidepressant plus placebo on white matter integrity as indexed by change in quantitative anisotropy (QA).; QA has no units but is measured from 0 to 1 and a higher indicates better white matter integrity
Fractional Anisotropy	12 weeks	The investigators will measure the impact of an antidepressant plus clemastine (5.36 mg twice daily) compared to antidepressant plus placebo on white matter integrity as indexed by change in fractional anisotropy (FA).; FA has no units but is measured from 0 to 1 and a higher indicates better white matter integrity

Secondary Outcome Measures

Name	Time	Method
Trail Making Test Part A and Part B	12 weeks	The investigators will examine the effectiveness of an antidepressant plus clemastine (5.36 mg twice daily) compared to antidepressant plus placebo on cognitive outcomes as indexed by Trail Making Test Parts A and B.; The Trail Making Test A and B is scored by the time to completion (seconds) and number of errors, with higher scores indicating worse performance.; For TMT Part A and Part B, the "average" and "deficient" scores are categorized as follows: TMT Part A 29 seconds (average) Over 79 seconds (Deficient) TMT Part B 75 seconds (average) Over 273 seconds (Deficient)
Orientation Dispersion Index	12 weeks	The investigators will measure the impact of an antidepressant plus clemastine (5.36 mg twice daily) compared to antidepressant plus placebo on white matter integrity as indexed by change in neurite orientation dispersion and density imaging (NODDI)-derived orientation dispersion index (ODI).; The ODI has no units but ranges from 0-1, with higher values indicating more neurite dispersion.
Neurite Density Index	12 weeks	The investigators will measure the impact of an antidepressant plus clemastine (5.36 mg twice daily) compared to antidepressant plus placebo on white matter integrity as indexed by change in neurite orientation dispersion and density imaging (NODDI)-derived measured neurite density index (NDI).; The NDI has no units but ranges from 0-1, with higher values indicating more intracellular diffusion