Hydroxychloroquine in Primary Progressive Multiple Sclerosis
Condition: Multiple Sclerosis, Primary Progressive
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this clinical trial is to determine if HCQ in a dose of 400mg daily can
      prevent worsening of walking ability in people PPMS. The number of participants in this study
      will be 35. A maximum of 42 people with PPMS will be included. The trial is funded through a
      private donation to the Hotchkiss Brain Institute MS Translational Clinical Trials Research
      Program and the University of Calgary. There is no sponsorship from the pharmaceutical
      industry.
    

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.
    

Intervention name(s): Hydroxychloroquine
Intervention type(s): Drug
Intervention description(s): Orally administered Hydroxychloroquine
Other intervention name(s): Plaquenil
Intervention MeSH terms: Hydroxychloroquine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment