DepressionPhase 2CLIMBNCT06591091
Clemastine for Improving White Matter and Boosting Antidepressant Response in Late-life Depression
A Phase 2 study testing Clemastine Fumarate in people with Depression, run by University of Illinois Chicago at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Depression
- What is being tested?
- Clemastine Fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Dec 2025to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Illinois College of Medicine
Chicago, Illinois, 60612
Olusola Ajilore, MD, PhD, 312-413-4562, oajilore@uic.edu
About this study
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.
Read the 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.
- Conditions
- Depression
- Being tested
- Clemastine Fumarate, Placebo
- Keywords
- Late-life Depression, Antidepressant medication response
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clemastine FumarateDrug
Also called Clemastine, Tavist Allergy
Listed in arm/group description
PlaceboDrug
Listed in arm/group description
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 12 weeks
Secondary outcomes (3)
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)
Measured: 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.
Measured: 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
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start10 Dec 2025
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of Illinois ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Illinois Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- Cures Within Reach
- Responsible party
- Principal investigator, Olusola Alade Ajilore, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06591091
- Sponsor's protocol ID
- 2024-0636
- Acronym
- CLIMB
- Status last verified
- Aug 2025
- First submitted
- 5 Aug 2024
- Last updated
- 30 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All deidentified data will made available upon request.
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.
PubMed 29029896Caverzasi 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.
PubMed 37155847Marawi 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.
PubMed 37598228
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clemastine for Improving White Matter and Boosting Antidepressant Response in Late-life Depression
- ClinicalTrials.gov ID
- NCT06591091
- Acronym / sponsor ID
- CLIMB / 2024-0636
- Conditions
- Depression
- Keywords
- Late-life Depression, Antidepressant medication response
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of Illinois ChicagoUniversity, hospital or other
- Collaborators
- Cures Within Reach
- Study start
- 10 Dec 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Clemastine arm | Experimental | Drug: Clemastine FumarateParticipants 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 comparator | Drug: PlaceboParticipants in the placebo arm of the study will receive a placebo capsule PO twice daily for 12 weeks. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clemastine FumarateAlso: Clemastine, Tavist AllergyListed in arm/group description | Drug | Clemastine arm |
| PlaceboListed in arm/group description | Drug | Placebo arm |
Primary outcome
Frequency, Intensity and Burden of Side Effects Rating Scale
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
3 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2026.
- Background: PubMed 29029896Green 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.
- Background: PubMed 37155847Caverzasi 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.
- Background: PubMed 37598228Marawi 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.
- Individual participant dataSharing planned: Yes. All deidentified data will made available upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clemastine Fumarate in people with Depression, run by University of Illinois Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Olu A Ajilore, MD, PhD (312-413-4562, oajilore@uic.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency, Intensity and Burden of Side Effects Rating Scale (time frame: 12 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06591091, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2026.