The DMPFC as a target in treatment-resistant Bulimia Nervosa and Anorexia Nervosa:investigating target engagement, dosing, reliability and duration of effect using rTMS, fMRI,and a sham controlled arm

Information

  • Research Project
  • 9227906
  • ApplicationId
    9227906
  • Core Project Number
    R61MH110034
  • Full Project Number
    1R61MH110034-01A1
  • Serial Number
    110034
  • FOA Number
    RFA-MH-16-406
  • Sub Project Id
  • Project Start Date
    6/1/2017 - 7 years ago
  • Project End Date
    4/30/2022 - 2 years ago
  • Program Officer Name
    CHAVEZ, MARK
  • Budget Start Date
    6/1/2017 - 7 years ago
  • Budget End Date
    4/30/2018 - 6 years ago
  • Fiscal Year
    2017
  • Support Year
    01
  • Suffix
    A1
  • Award Notice Date
    5/23/2017 - 7 years ago

The DMPFC as a target in treatment-resistant Bulimia Nervosa and Anorexia Nervosa:investigating target engagement, dosing, reliability and duration of effect using rTMS, fMRI,and a sham controlled arm

PROJECT SUMMARY This project investigates the utility of dorsomedial prefrontal cortex(DMFPC) repetitive transcranial magnetic stimulation (rTMS) in bingeing and purging in chronic, treatment- resistant bulimia nervosa(BN), and anorexia nervosa, binge-purging subtype(ANBN). rTMS uses powerful, focused magnetic field pulses to change activity in target brain regions. Published pilot work shows 57% of those treated with DMPFC rTMS for bingeing and purging experience both a >50% reduction in both bingeing and purging, and a wide variety of improvements in other domains, including mood, anxiety, and affective regulation. Response in terms of reduced bingeing and purging does not appear to be correlated to other comorbidity. Response is heavily correlated to pre-treatment fronto- striatal connectivity as measured by functional magnetic resonance imaging(frmi), where responders have a consistent pattern of poor connectivity initially compared to non- responders, which pattern normalizes over the course of treatment The aims of the proposed R61/33 phased trial are to 1) confirm target engagement and determine an optimal dosing paradigm(R61 phase); and 2) ensure that the results are not due to a placebo effect, determine the clinical effectiveness and duration of effect, and begin to examine the potential use of pre-treatment fMRI as a biomarker of treatment suitability(R33 phase). Subjects in the R61 arm will undergo 30 bilateral rTMS treatments accompanied by a suite of imaging, clinical, psychometric, and psychological test assessments, in two dosage regimens and a sham arm. In the R33 phase, the optimal dosing regimen will be used with a novel active/sham coil to administer 20 rTMS treatments in a triple blind design. Subjects will again be assessed as in the R61 phase. If successful, the study will provide evidence for the future development of rTMS as a novel, effective treatment for refractory BN and ANBP, and further information as to the neural mechanisms both of the illnesses and the mechanism of response to rTMS.

IC Name
NATIONAL INSTITUTE OF MENTAL HEALTH
  • Activity
    R61
  • Administering IC
    MH
  • Application Type
    1
  • Direct Cost Amount
    403568
  • Indirect Cost Amount
    32285
  • Total Cost
    435853
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    242
  • Ed Inst. Type
  • Funding ICs
    NIMH:435853\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZMH1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    UNIVERSITY HEALTH NETWORK
  • Organization Department
  • Organization DUNS
    208469486
  • Organization City
    TORONTO
  • Organization State
    ON
  • Organization Country
    CANADA
  • Organization Zip Code
    M5G 2M9
  • Organization District
    CANADA