Multiple Sclerosis, Primary ProgressivePhase 2NCT02913157
Hydroxychloroquine in Primary Progressive Multiple Sclerosis
A Phase 2 study testing Hydroxychloroquine in people with Multiple Sclerosis, Primary Progressive, run by University of Calgary at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis, Primary Progressive
- What is being tested?
- Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2016to Jun 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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.
- Conditions
- Multiple Sclerosis, Primary Progressive
- Being tested
- Hydroxychloroquine
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Plaquenil
Orally administered Hydroxychloroquine
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine | Experimental | Oral Hydroxychloroquine, 200mg BID Receives: Drug: Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Timed 25-Foot Walk (T25FW)
quantitative ambulation performance test
Measured: Change in Timed 25-Foot Walk performance between the 6 month and 18 month visit.
Secondary outcomes (5)
9-Hole Peg Test
Brief, standardized, quantitative test of upper extremity
Measured: baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
Symbol Digit Modalities Test
measures cognitive processing speed and working memory
Measured: 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)
standard measure of neurologic impairment that is used to describe disability in MS. The neurological assessment comprises seven functional system
Measured: baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
Modified Fatigue Impact Scale (MFIS)
structured, self-report questionnaire with 21 items concerning how fatigue impact patients quality of life
Measured: 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
54-item multidimensional health-related quality of life measure that combines both generic and MS-specific items
Measured: baseline, 1 month follow-up, 6 months follow-up, 12 months follow-up, and 18 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2016 (estimated)
- Study startNov 2016
- Primary completionJun 2021
- Study completionJun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Primary ProgressiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Marcus Werner Koch, University of Calgary
- Investigators
- Marcus Koch, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02913157
- Sponsor's protocol ID
- HCQ_MS01
- Status last verified
- Jul 2021
- First submitted
- 20 Sep 2016
- Last updated
- 30 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
Baeva ME, Tottenham I, Koch M, Camara-Lemarroy C. Biomarkers of disability worsening in inactive primary progressive multiple sclerosis. J Neuroimmunol. 2024 Feb 15;387:578268. doi: 10.1016/j.jneuroim.2023.578268. Epub 2023 Dec 23.
PubMed 38157653Camara-Lemarroy C, Silva C, Gohill J, Yong VW, Koch M. Serum neurofilament-light and glial fibrillary acidic protein levels in hydroxychloroquine-treated primary progressive multiple sclerosis. Eur J Neurol. 2023 Jan;30(1):187-194. doi: 10.1111/ene.15588. Epub 2022 Oct 25.
PubMed 36214614Brown D, Moezzi D, Dong Y, Koch M, Yong VW. Combination of Hydroxychloroquine and Indapamide Attenuates Neurodegeneration in Models Relevant to Multiple Sclerosis. Neurotherapeutics. 2021 Jan;18(1):387-400. doi: 10.1007/s13311-020-01002-5. Epub 2021 Jan 6.
PubMed 33410109
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02913157
- Acronym / sponsor ID
- HCQ_MS01
- Conditions
- Multiple Sclerosis, Primary Progressive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- Nov 2016 (actual)
- Primary completion
- Jun 2021 (actual)
- Study completion
- Jun 2021 (actual)
- First posted
- 23 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine | Experimental | Drug: HydroxychloroquineOral Hydroxychloroquine, 200mg BID |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxychloroquineAlso: PlaquenilOrally administered Hydroxychloroquine | Drug | Hydroxychloroquine |
Primary outcome
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
5 secondary outcomes
9-Hole Peg Test
Time frame: 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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
- Derived from this study: PubMed 38157653Baeva ME, Tottenham I, Koch M, Camara-Lemarroy C. Biomarkers of disability worsening in inactive primary progressive multiple sclerosis. J Neuroimmunol. 2024 Feb 15;387:578268. doi: 10.1016/j.jneuroim.2023.578268. Epub 2023 Dec 23.
- Derived from this study: PubMed 36214614Camara-Lemarroy C, Silva C, Gohill J, Yong VW, Koch M. Serum neurofilament-light and glial fibrillary acidic protein levels in hydroxychloroquine-treated primary progressive multiple sclerosis. Eur J Neurol. 2023 Jan;30(1):187-194. doi: 10.1111/ene.15588. Epub 2022 Oct 25.
- Derived from this study: PubMed 33410109Brown D, Moezzi D, Dong Y, Koch M, Yong VW. Combination of Hydroxychloroquine and Indapamide Attenuates Neurodegeneration in Models Relevant to Multiple Sclerosis. Neurotherapeutics. 2021 Jan;18(1):387-400. doi: 10.1007/s13311-020-01002-5. Epub 2021 Jan 6.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marcus Koch principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydroxychloroquine in people with Multiple Sclerosis, Primary Progressive, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Timed 25-Foot Walk (T25FW) (time frame: Change in Timed 25-Foot Walk performance between the 6 month and 18 month visit.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02913157, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2021.