Clinical Trial: Pharmacokinetics of DMF and the Effects of DMF on Exploratory Biomarkers

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open Label Study of the Pharmacokinetics of DMF and the Effects of DMF on Exploratory Biomarkers in Subjects With Secondary Progressive Multiple Sclerosis

Brief Summary: The purpose of this study is to explore whether DMF (Dimethyl Fumarate) or MMF (monomethyl fumarate) its main bioactive metabolite, is capable of entering the central nervous system in SPMS patients that are being treated with Tecfidera®. PK samples (pharmacokinetics - or the amount of study drug in blood) will be tested to compare with PK samples, the amount of study drug, in spinal fluid (CSF).

Detailed Summary:
Sponsor: Multiple Sclerosis Center of Northeastern New York

Current Primary Outcome:

  • The primary objective of the study is to investigate the PK (drug level) of DMF(study drug) in CSF with SPMS. [ Time Frame: post-DMF treatment in Week 6 ]
    Concentration of DMF in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
  • The primary objective of the study is to investigate the PK (drug level) of DMF(study drug) in plasma in subjects with SPMS. [ Time Frame: treatment in week 6 ]
    Concentration of DMF in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
  • The primary objective of the study is to investigate the PK (drug level) of MMF(the primary metabolite of study drug) in CSF with SPMS. [ Time Frame: treatment in week 6 ]
    Concentration of MMF in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
  • The primary objective of the study is to investigate the PK (drug level) of MMF( the primary metabolite of study drug) in plasma in subjects with SPMS. [ Time Frame: treatment in week 6 ]
    Concentration of MMF in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6
  • The primary objective of the study is to investigate the PK (drug level) of DMF conjugate (study drug) in CSF with SPMS. [ Time Frame: treatment in week 6 ]
    Concentration of DMF conjugate in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6.
  • The primary objective of the study is to investigate the PK (drug level) of DMF conjugate (study drug) in

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • A secondary objective is to assess the effects of DMF on PD biomarkers downstream of Nrf2 in the CSF of subjects with SPMS. [ Time Frame: at 28 weeks ]
      PD biomarkers downstream of Nrf2, such as NAD(P)H hydrogenase [quinone 1], heme oxygenase-1, and aldo-keto reductase family 1 member B8 that have not been evaluated in CNS.
    • A secondary objective is to assess the effects of DMF on biomarkers of inflammation in the CSF of subjects with SPMS. [ Time Frame: at 28 weeks ]
      Biomarkers of inflammation (e.g., osteopontin, B cell activating factor, chemokines, and matrix metalloproteinase 9), which may reflect pathogenesis in SPMS.
    • A secondary objective is to assess the effects of DMF on biomarkers of neuroaxonal damage in the CSF of subjects with SPMS. [ Time Frame: at 28 weeks ]
      Biomarkers of neuroaxonal damage (e.g., neurofilament, myelin basic protein, glial fibrillary acidic protein, and neural cell adhesion molecule), which may reflect pathogenesis in SPMS.
    • A secondary objective is to assess the effects of DMF on biomarkers of oxidative stress in the CSF of subjects with SPMS. [ Time Frame: at 28 weeks ]
      Biomarkers of oxidative stress (e.g., myeloperoxidase, 8-Oxo-2'-deoxyguanosine and RNA biomarkers), which may reflect pathogenesis in SPMS
    • A secondary objective is to assess the effects of DMF on myelin lipid biomarkers in the CSF of subjects with SPMS. [ Time Frame: at 28 weeks ]
      Myelin lipid biomarkers (e.g., cholesterol, galactoceramide, sulfatides, and sphingomyelin), which may correlate with disability progression in MS patients.
    • A secondary objective is to assess the effects of DMF on pharmacogenomic biomarkers in the CSF of subjects with SPMS. [ Time Frame: at 28 weeks ]
      Pharmacogenomic biomarkers: DNA analysis from blood samples.
    • A secondary objective is to assess the effects of DMF on RNA samples from CSF cellular pellet for transcriptionomics in the CSF of subjects with SPMS. [ Time Frame: at 28 weeks ]
      RNA samples from CSF cellular pellet for transcriptionomics.


    Original Secondary Outcome: Same as current

    Information By: Multiple Sclerosis Center of Northeastern New York

    Dates:
    Date Received: January 14, 2016
    Date Started: August 2015
    Date Completion:
    Last Updated: March 21, 2017
    Last Verified: March 2017