Clinical Trial: Pilot Trial of Domperidone in Relapsing-Remitting Multiple Sclerosis (RRMS)

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: Randomized, Controlled Pilot Trial of Domperidone in Relapsing-Remitting Multiple Sclerosis

Brief 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

Detailed Summary:

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
  Sponsor: University of Calgary
  

  Current Primary Outcome: Measures of repair within enhancing T1 MRI lesions [ Time Frame: up to 32 weeks ]

  Texture analysis, Diffusion Tensor Imaging (DTI) and Magnetization Transfer Imaging (MTI) will be used. This is a pilot study so the investigators are measuring repair at 2 time points and with 3 imaging methods to aid in the design of future studies.
  
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome:

  • Number and type of adverse events over the 16 week treatment period. [ Time Frame: at 6 and 16 weeks ]
    Adverse events will be collected at all visits and by telephone if an encounter occurs. Clinical outcomes are not sufficiently sensitive or specific to stand as measures of repair in phase 2 clinical trials that aim to screen therapies for their potential to provide neuroprotection or enhance repair. Therefore the investigators will only use clinical measures at the baseline visit to describe participants with regards to level of clinical impairment. The investigators will use the standard measure of clinical impairment, the EDSS. The baseline neurological examination and EDSS will also be used to confirm the occurrence of a relapse. A relapse that occurs during the treatment period in a participant on domperidone will be considered an adverse event. Enhancing lesions on MRI after baseline will also be considered adverse events.
  • Serum Prolactin Levels at both 6 and 16 weeks [ Time Frame: at 6 and 16 weeks ]
    To determine how much domperidone 10mg three times daily increases serum prolactin levels in this MS population over time. The investigators will also explore the relationship between prolactin level and repair.
  
  
  

  Original Secondary Outcome: Same as current
  
  Information By: University of Calgary
  

  Dates:
  Date Received: July 2, 2015
  Date Started: August 2015
  Date Completion: August 2018
  Last Updated: February 23, 2017
  Last Verified: February 2017