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

NCT06591091 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 2024-0636
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

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

Keywords

Late-life Depression; Antidepressant medication response

Outcome Measures

Primary Outcomes (4)

• Frequency, Intensity and Burden of Side Effects Rating Scale

  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

  12 weeks

• Montgomery-Asberg Rating Scale for Depression

  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

  12 weeks

• Quantitative Anisotropy

  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

  12 weeks

• Fractional Anisotropy

  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

  12 weeks

Secondary Outcomes (3)

• Trail Making Test Part A and Part B

  12 weeks

• Orientation Dispersion Index

  12 weeks

• Neurite Density Index

  12 weeks

Study Arms (2)

Clemastine arm

EXPERIMENTAL

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.

Drug: Clemastine Fumarate

Placebo arm

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Clemastine Fumarate DRUG

Listed in arm/group description

Also known as: Clemastine, Tavist Allergy

Clemastine arm

Placebo DRUG

Listed in arm/group description

Placebo arm

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• Cures Within Reach: collaborator

Related Publications (3)

• Green AJ, Gelfand JM, Cree BA, Bevan C, Boscardin WJ, Mei F, Inman J, Arnow S, Devereux M, Abounasr A, Nobuta H, Zhu A, Friessen M, Gerona R, von Budingen HC, Henry RG, Hauser SL, Chan JR. Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial. Lancet. 2017 Dec 2;390(10111):2481-2489. doi: 10.1016/S0140-6736(17)32346-2. Epub 2017 Oct 10.

  PMID: 29029896 BACKGROUND

• Caverzasi E, Papinutto N, Cordano C, Kirkish G, Gundel TJ, Zhu A, Akula AV, Boscardin WJ, Neeb H, Henry RG, Chan JR, Green AJ. MWF of the corpus callosum is a robust measure of remyelination: Results from the ReBUILD trial. Proc Natl Acad Sci U S A. 2023 May 16;120(20):e2217635120. doi: 10.1073/pnas.2217635120. Epub 2023 May 8.

  PMID: 37155847 BACKGROUND

• Marawi T, Ainsworth NJ, Zhukovsky P, Rashidi-Ranjbar N, Rajji TK, Tartaglia MC, Voineskos AN, Mulsant BH. Brain-cognition relationships in late-life depression: a systematic review of structural magnetic resonance imaging studies. Transl Psychiatry. 2023 Aug 19;13(1):284. doi: 10.1038/s41398-023-02584-2.

  PMID: 37598228 BACKGROUND

MeSH Terms

Conditions

Depression

Interventions

Clemastine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Olu A Ajilore, MD, PhD

CONTACT

312-413-4562; oajilore@uic.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The design of this pilot study is a randomized double-blind. Only the study Pharmacist will be unblinded to the placebo-controlled design.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor. Director, Clinical Research Core/Center for Clinical and Translational Science

Model Details: The design of this pilot study is a randomized double-blind, placebo-controlled design with one arm standard antidepressant treatment plus placebo (n=20) and one arm standard antidepressant treatment plus clemastine (5.36 mg PO daily; n=60) for 12 weeks with primary outcomes related to improvement in the level of depression and white matter integrity.

Study Record Dates

• First Submitted: August 5, 2024
• First Posted: September 19, 2024
• Study Start: September 1, 2025
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: The data will be available approximately one year after the study is completed and will be available for the duration specified by the Sponsor.