Hydroxychloroquine in Primary Progressive Multiple Sclerosis
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|ClinicalTrials.gov Identifier: NCT02913157|
Recruitment Status : Active, not recruiting
First Posted : September 23, 2016
Last Update Posted : February 24, 2020
|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis, Primary Progressive||Drug: Hydroxychloroquine||Phase 2|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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)|
|Actual Study Start Date :||November 2016|
|Estimated Primary Completion Date :||October 2020|
|Estimated Study Completion Date :||December 2020|
Oral Hydroxychloroquine, 200mg BID
Orally administered Hydroxychloroquine
Other Name: Plaquenil
- 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
- 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
- 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
- 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 ]standard measure of neurologic impairment that is used to describe disability in MS. The neurological assessment comprises seven functional system
- 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
- 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02913157
|MS Clinic Foothills Medical Centre|
|Calgary, Alberta, Canada, T2N2T9|
|Principal Investigator:||Marcus Koch||University of Calgary|