- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02913157
Hydroxychloroquine in Primary Progressive Multiple Sclerosis
Open-label, Single-center, Single-arm Futility Trial Evaluating Oral Hydroxychloroquine 200mg BID for Reducing Progression of Disability in Patients With Primary Progressive Multiple Sclerosis (PPMS)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
In patients with primary progressive multiple sclerosis (PPMS) there is ongoing slow and continuous loss of nerve cells, which causes damage to the brain and spinal cord. This ultimately becomes noticeable as slowly and continuously worsening disability. While the cause of this ongoing damage is unknown, it appears that at least part of the damage may be caused by cells in the brain called "microglia" (a type of immune cell that reside in the brain and spinal cord). These microglial cells can have beneficial roles, for instance when they clear away debris, but they can also cause damage to brain cells. In PPMS, microglial cells are often found to be in a state of activation, and it is currently believed that this constant activation of microglial cells is likely an important cause of the ongoing damage to brain cells.
Current treatments for MS only work in relapsing-remitting MS, and can prevent relapses, but so far there are no treatments that effectively target PPMS. Therapies for PPMS are needed. The investigators believe that treatments that target and reduce the activation of microglial cells may be a useful treatment strategy.
Hydroxychloroquine (HCQ) is a medication that has been shown to decrease the activity of human microglia in laboratory experiments. Animal experiments have also shown that treatment with HCQ can reduce the disease activity of an animal model of MS. HCQ, therefore, may also reduce the activity of microglia in people with PPMS, and hopefully prevent or slow down the progression of disability in PPMS.
HCQ is currently approved in Canada to treat malaria and the rheumatic diseases Systemic Lupus Erythematodes (SLE) and Rheumatoid Arthritis (RA). HCQ is available as a tablet that is usually taken two times per day. Doses up to 600mg per are used in clinical practice, but the investigators estimate that a dose of only 400mg daily, given as two doses of 200mg, will be sufficient to decrease the activity of microglia in patients with PPMS. HCQ is usually well tolerated.
Following a MinMax Simon-2-stage design, the study will require 35 patients with complete 18 month follow-up. Presuming 20% drop-out, the investigators anticipate recruiting up to 42 patients. The trial will be conducted as follows: patients will continuously enter into the study until 35 patients have completed 18 months of follow-up with at least 75% adherence which will be measured by study drug count.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Alberta
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Calgary, Alberta, Canada, T2N2T9
- MS Clinic Foothills Medical Centre
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent obtained
- Men and women aged of 18 and 65 years inclusive
- Who are followed at the Calgary MS Clinic
- With Primary Progressive Multiple Sclerosis, according to current diagnostic criteria
- Screening Expanded Disability Status Scale score between 4.0 and 6.5 inclusive.
- Screening timed 25 foot walk (average of two trials) of 5.5 seconds or more.
Exclusion Criteria:
- Patients undergoing treatment with antimalarial drugs, amiodarone, dapsone or digoxin
- Patients with known retinopathy
- Patients whose screening ophthalmological exam shows retinopathy
- Patients whose screening MRI scan shows gadolinium enhancing lesions
- Patients with known renal insufficiency
- Patients with known significant hepatic impairment
- Patients with known porphyria
- Patients with known allergy or other intolerability to HCQ, or to gadolinium MRI contrast agent
- Patients currently using Fampridine or 4-aminopyridine
- Patients planning to start Fampridine or 4-aminopyridine during the study period
- Patients planning to start Baclofen or Tizanidine during the duration of the study
- Patients who increase the dose of Baclofen or Tizanidine during the study period
- Patients who receive treatment with Botulinum toxin in the leg muscles during the study period
- Patients using amiodarone, dapsone, digoxin or antimalarial drugs other than HCQ
- Patients who are unable or unwilling to undergo gadolinium enhanced MRI scans
- Pregnant or breast-feeding women
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Hydroxychloroquine
Oral Hydroxychloroquine, 200mg BID
|
Orally administered Hydroxychloroquine
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Timed 25-Foot Walk (T25FW)
Time Frame: Change in Timed 25-Foot Walk performance between the 6 month and 18 month visit.
|
quantitative ambulation performance test
|
Change in Timed 25-Foot Walk performance between the 6 month and 18 month visit.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
9-Hole Peg Test
Time Frame: baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
|
Brief, standardized, quantitative test of upper extremity
|
baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
|
Symbol Digit Modalities Test
Time Frame: baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
|
measures cognitive processing speed and working memory
|
baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
|
Multiple Sclerosis Quality of Life Scale 54 item version
Time Frame: baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
|
54-item multidimensional health-related quality of life measure that combines both generic and MS-specific items
|
baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
|
Functional Systems and Expanded Disability Status Scale (EDSS)
Time Frame: baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
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standard measure of neurologic impairment that is used to describe disability in MS.
The neurological assessment comprises seven functional system
|
baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
|
Modified Fatigue Impact Scale (MFIS)
Time Frame: baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
|
structured, self-report questionnaire with 21 items concerning how fatigue impact patients quality of life
|
baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Marcus Koch, University of Calgary
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Multiple Sclerosis
- Multiple Sclerosis, Chronic Progressive
- Sclerosis
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Hydroxychloroquine
Other Study ID Numbers
- HCQ_MS01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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