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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression
• Intervention / Treatment: Drug: Clemastine Fumarate; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Olu A Ajilore, MD, PhD; Phone Number: 312-413-4562; Email: oajilore@uic.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Clemastine Fumarate; Listed in arm/group description; Other Names: Clemastine; Tavist Allergy
Placebo Comparator: Placebo arm; Participants in the placebo arm of the study will receive a placebo capsule PO twice daily for 12 weeks.	Drug: Placebo; Listed in arm/group description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trail Making Test Part A and Part B	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)	12 weeks
Orientation Dispersion Index	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.	12 weeks
Neurite Density Index	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	12 weeks

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: Cures Within Reach

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: August 5, 2024
• First Submitted That Met QC Criteria: September 6, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Late-life Depression; Antidepressant medication response
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Substandard Drugs; Pharmaceutical Preparations; Pyrrolidines; Clemastine; Counterfeit Drugs
• Other Study ID Numbers: 2024-0636

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All deidentified data will made available upon request.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No