Titre officiel
Open-label, Single-centre, Single-arm Futility Trial Evaluating the Combination of Oral Hydroxychloroquine 200mg BID and Indapamide 2.5mg OD for Reducing Progression of Disability in People With Secondary Progressive Multiple Sclerosis (SPMS)
Sommaire:
L’objectif de cet essai clinique est de
déterminer si l’administration d’hydroxychloroquine (HCQ) à raison de
400 mg par jour et d’indapamide à raison de 2,5 mg par jour peut
contribuer à réduire la progression de l’invalidité chez les personnes
atteintes d’une sclérose en plaques progressive secondaire.
Le nombre de participants à cette étude
sera de 35. Au maximum, 42 personnes atteintes d’une sclérose en
plaques progressive secondaire seront incluses. L’essai bénéficie du
financement interne de l’Université de Calgary. Il ne bénéficie du parrainage d’aucune
industrie pharmaceutique.
Description de l'essai
Primary Outcome:
- Timed 25-Foot Walk (T25FW)
Secondary Outcome:
- 9-Hole Peg Test
- Symbol Digit Modalities Test
- Functional Systems and Expanded Disability Status Scale (EDSS)
- Modified Fatigue Impact Scale (MFIS)
- Multiple Sclerosis Quality of Life Scale 54 item version
In
patients with SPMS, 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 resides 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 SPMS, 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. Another harmful process affecting patients with SPMS is
"oxidative stress". Oxidative stress occurs when immune cells in the
brain and spinal cord are activated and produce substances that may
damage nerve cells. Current treatments for MS mostly are meant to
prevent relapses and are beneficial in relapsing-remitting MS, but so
far there are no treatments that benefit people with SPMS who do not
experience relapses. Better therapies are needed for SPMS, and it is
believed that treatments that reduce the activation of microglial cells
and oxidative stress may be useful.
The medication
Hydroxychloroquine (HCQ) reduces the activity of human microglia in
laboratory experiments. Animal experiments also showed that treatment
with HCQ reduces disease severity in an animal model of MS. HCQ,
therefore, may also reduce the activity of microglia in people with
SPMS, and hopefully prevent or slow down the progression of disability
in SPMS. HCQ is currently approved in Canada to treat malaria and
rheumatic diseases Systemic Lupus Erythematosus (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
it is estimated 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 SPMS. HCQ is usually well tolerated.
Indapamide (IND) is a
medication to treat high blood pressure that can reduce oxidative stress
and improve the survival of nerve cells in laboratory studies. IND is
currently approved to treat high blood pressure. IND is available in
tablet form and is usually taken once a day, the most typical dose is
2.5mg. It is estimated that a dose of 2.5mg per day will be sufficient
to treat oxidative stress in SPMS. IND is usually well tolerated.
Following a MinMax
Simon-2-stage design, the study will require 35 patients with a 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.
Voir cet essai sur ClinicalTrials.gov
