Clinical trial NCT06591091: Clemastine for Improving White Matter and Boosting Antidepressant Response in Late-life Depression
Official title: Clemastine for Improving White Matter and Boosting Antidepressant Response in Late-life Depression
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Depression
Keywords: Late-life Depression
Antidepressant medication response
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: Cures Within Reach
First posted: 2024-09-19
Enrollment: 80
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Frequency, Intensity and Burden of Side Effects Rating Scale
timeFrame: 12 weeks
measure: Montgomery-Asberg Rating Scale for Depression
timeFrame: 12 weeks
measure: Quantitative Anisotropy
timeFrame: 12 weeks
measure: Fractional Anisotropy
timeFrame: 12 weeks
Secondary outcomes:
measure: Trail Making Test Part A and Part B
timeFrame: 12 weeks
measure: Orientation Dispersion Index
timeFrame: 12 weeks
measure: Neurite Density Index
timeFrame: 12 weeks
Other outcomes:
Locations:
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.