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

Overview

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.

Interventions

• Drug Clemastine Fumarate
  Listed in arm/group description
• Drug Placebo
  Listed in arm/group description

Primary outcome measures

• 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]

Secondary outcome measures (3)

• Trail Making Test Part A and Part B [Time frame: 12 weeks]
• Orientation Dispersion Index [Time frame: 12 weeks]
• Neurite Density Index [Time frame: 12 weeks]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Illinois College of Medicine — Chicago

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 PMID 29029896
• 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
• 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

Identifiers

NCT: NCT06591091 · 2024-0636

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗