Pilot Trial of Domperidone in Relapsing-Remitting Multiple Sclerosis (RRMS)
Condition: Multiple Sclerosis, Relapsing-Remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      The first major objective of this pilot trial is to demonstrate that it is possible to study
      myelin repair in relapsing-remitting multiple sclerosis (RRMS) patients with enhancing
      lesions on MRI by using advanced imaging techniques. To demonstrate that this is possible the
      investigators will recruit 24 RRMS patients who are being treated with standard disease
      modifying therapy (DMT) and have new lesions identified on clinically indicated brain MRI
      scans and measure myelin repair at 16 and 32 weeks using MRI measures of myelin repair. The
      second major objective is to determine how much repair occurs in participants treated with
      domperidone compared with those who are not treated. This will allow us to design larger
      trials to confirm that domperidone improves repair. The study will also confirm the safety
      and tolerability of domperidone in RRMS, determine circulating prolactin levels during dosing
      with domperidone 10mg three times daily in people with RRMS, and explore the impact of other
      clinical factors (such as age) on lesion repair.

      In addition, blood will be collected to test for metabolomics and the investigators will bank
      blood for future study of biomarkers that can help the investigators better understand MS.
      Metabolomics is an experimental test where changes in the pattern of the chemicals in blood
      cells are compared at different time points (during and after inflammation). There will be
      random changes but changes that are common in most study participants may help identify
      chemicals that signal stages in injury or repair. The investigators will also compare the
      pattern of change in those with the best repair to those with the worst repair. This may help
      identify a chemical that is associated with better or worse repair and help develop new
      treatment strategies. There are currently no blood tests that help in the diagnosis of MS,
      help determine which drug a person will respond to, or help determine a person's expected MS
      outcome. Any such tests would be considered biomarkers.
    

Detailed description: 
      Primary Objectives:

        -  To demonstrate that the investigators can recruit DMT treated RRMS patients who have
           breakthrough enhancing lesions identified on clinically indicated monitoring brain MRI
           scans and measure lesion repair over 32 weeks.

        -  To obtain estimates of the magnitude and variability of lesion repair in DMT treated
           RRMS patients who are taking add-on domperidone, or no add-on treatment. The
           investigators will evaluate three MRI measures [texture analysis, diffusion tensor
           imaging (DTI), and magnetization transfer imaging (MTI)] for their ability to measure
           repair within acute enhancing lesions in RRMS. They will also evaluate repair at 16 and
           32 weeks. These outcomes will aid in the development of future trials.

      No therapies have yet been shown to improve lesion repair, and there is no accepted trial
      model to evaluate lesion repair in humans. Therefore, the investigators anticipate that the
      data from this trial will inform the design of future phase 2 trials of therapies to promote
      lesion repair in MS.

      Secondary Objectives:

        -  To determine the safety and tolerability of domperidone in RRMS

        -  To determine serum prolactin levels during dosing with domperidone 10mg tid in this
           population

        -  To explore metabolomic profiling during lesion repair.

        -  To explore the impact of the following variables on lesion repair: prolactin level at 6
           weeks, concurrent use of each type of DMT, Vitamin D and B12 levels at baseline, patient
           clinical characteristics (MS duration, EDSS), imaging characteristics (T2 lesion volume,
           enhancing lesion volume), patient demographics and behaviours (age, sex, smoking
           status).
    

Intervention name(s): Domperidone
Intervention type(s): Drug
Intervention description(s): Addition of Domperidone to current Disease Modifying Therapy.
Other intervention name(s): domperidone maleate
Intervention MeSH terms: Domperidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Multiple Sclerosis; Domperidone; Relapsing-Remitting MS; Demyelinating disease; Remyelination