Safety of Maraviroc for Post-stroke Depression

Study Overview
=================
Brief Summary
-----------------
Post-stroke depression (PSD) is a barrier to effective rehabilitation and recovery after stroke. Current treatment options are limited and there is an unmet need for specific and effective therapeutic options. Objective: To examine the safety and efficacy of Maraviroc, a CCR5 antagonist, as a possible add-on treatment option for PSD, in an open-labeled proof-of-concept clinical trial. Design, Setting, and Participants: A 10-week trial of daily oral 300 mg Maraviroc in ten patients with subcortical stroke suffering from PSD. Follow-up: eight weeks after completing treatment. Main Outcome Measure: A change in the Montgomery-Asberg Depression Rating Scale (MADRS).

Official Title
-----------------
Safety of Maraviroc for Post-stroke Depression (Proof-of-concept)

Conditions
-----------------
Post-stroke Depression

Intervention / Treatment
-----------------
* Drug: Maraviroc 300 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Men and women aged 50 to 86 years; Able to fully comprehend and sign an informed consent form; Diagnosis of stroke/TIA prior to study entrance and evidence of ischemic infarct and/or lacunar infarcts on MRI (defined as sharply demarcated hypointense lesions <20mm on T1-weighted images with corresponding hypointense lesions with hyperintense rim on FLAIR) and/or deep Cerebral Microbleeds (CMB) (defined as round hypointense lesions on T2-weighted gradient echo-images with a diameter < 10 mm in neuroimaging. Meet Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) diagnostic criteria for major depressive episode that developed up to 12 months after the documented stroke/TIA. Able to comply with scheduled visits, treatment plan, and other trial procedures; Treatment with other antidepressants is allowed but subjects will be asked not to change their regular treatment regime during the trial. Exclusion Criteria: Hemorrhages and cerebral edema (e.g., subarachnoid haemorrhage, intracerebral hemorrhage, subdural hematoma, epidural hematoma) Patients in a state of coma or with severe disturbance of consciousness, aphasia, agnosia, or deafness that subsequently affects expression and communication. Significant acute medical illness including: drug overdose, severely disturbed liver, kidney or lung function, anemia, hypothyroidism, or uncontrolled diabetes. Significant acute neurologic illness including: impaired consciousness, Parkinson's disease, Huntington's chorea, progressive supranuclear paralysis, brain tumor, subdural hematoma, multiple sclerosis, hydrocephalus, Binswanger's disease, or severe aphasia Patients diagnosed with dementia or major neurocognitive disorder as defined by DSM-5at screening, or other neurological conditions that might dominate the clinical picture (multiple sclerosis, Parkinson's disease, epilepsy, Huntington's chorea, progressive supranuclear paralysis, brain tumor, subdural hematoma, multiple sclerosis, hydrocephalus, Binswanger's disease, etc.) Subject has a history of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or elevated hepatic transaminases or bilirubin, or tests positive for HIV at Screening. History of renal insufficiency or serum creatinine over 1.6;; Subject has a current or past diagnosis of bipolar or related disorders, intellectual disability, cluster B personality disorder (e.g., borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder), psychotic disorder, schizophrenia, PTSD , and substance/alcohol use disorders other than nicotine in the past year (including barbiturates, methadone, opiates, cocaine, cannabinoids, and amphetamine/ methamphetamine). Subject has suicidal ideation with intent to act during the screening phase or on Day 1 per investigator's clinical judgment, or has a history of suicidal behavior within the past year; or subject has homicidal ideation/intent at Screening or on Day 1. Subject has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigatoris considered cured with minimal risk of recurrence). Subject has known allergies, hypersensitivity, intolerance, or contraindication to Maraviroc or its excipients. Subject has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 60 days before the planned first dose of study drug or is currently enrolled in an investigational study. Subject is a woman who is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study drug. Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. Subject has had major surgery, (e.g., requiring general anesthesia) within 2 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study. Use of drugs with possible interactions with Maraviroc.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 86 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maraviroc 300 mg/day<br>Open-label study | Drug: Maraviroc 300 mg<br>* 10 week treatment as add-on therapy to anti-depressants<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) | depression score | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 16-item quick inventory of depressive symptoms- self-report, QIDS-SR16 | self-report depression score | 10 weeks | 
| clinical global impression scale (CGI) | Clinician impression | 10 weeks | 
| 7-item patient-reported generalized anxiety disorder 7-item scale- GAD-7 | Anxiety score | 10 weeks |