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Hydroxychloroquine in Primary Progressive Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT02913157
Recruitment Status : Recruiting
First Posted : September 23, 2016
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
Dr. Marcus Werner Koch, University of Calgary

Tracking Information
First Submitted Date  ICMJE September 20, 2016
First Posted Date  ICMJE September 23, 2016
Last Update Posted Date April 16, 2019
Actual Study Start Date  ICMJE November 2016
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 21, 2016)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02913157 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2016)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hydroxychloroquine in Primary Progressive Multiple Sclerosis
Official Title  ICMJE 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)
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis, Primary Progressive
Intervention  ICMJE Drug: Hydroxychloroquine
Orally administered Hydroxychloroquine
Other Name: Plaquenil
Study Arms  ICMJE Experimental: Hydroxychloroquine
Oral Hydroxychloroquine, 200mg BID
Intervention: Drug: Hydroxychloroquine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 21, 2016)
35
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Marcus Koch 4032106790 mwkoch@ucalgary.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02913157
Other Study ID Numbers  ICMJE HCQ_MS01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Dr. Marcus Werner Koch, University of Calgary
Study Sponsor  ICMJE University of Calgary
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marcus Koch University of Calgary
PRS Account University of Calgary
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP