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Safety and Efficacy of Fremanezumab for Migraine in Adult CADASIL

Primary Purpose

Cadasil, Migraine

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Fremanezumab
Placebo
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cadasil

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  • Age 18 to 70 years old
  • English speaking
  • Diagnosis of CADASIL confirmed by presence of a pathogenic NOTCH3 gene mutation
  • Diagnosis of migraine for at least 12 months and diagnosis of chronic migraine for at least 28 days according to the International Classification of Headache Disorders
  • MIDAS score of >10 points
  • Ability to provide written informed consent

Exclusion Criteria

  • History of ischemic stroke within 4 weeks of screening assessment
  • Screening blood pressure >150 mm Hg
  • Use of onabotulinum toxin A 4 months prior to trial or other injectable/stimulatory/magnetic method of headache control
  • Use of opiates or barbiturates 4 days prior to trial
  • Patients with competing intracerebral pathology (e.g. history of intracerebral hemorrhage, multiple sclerosis)
  • NYHA Class III or IV congestive heart failure
  • History of myocardial infarction
  • History of coronary bypass surgery or coronary stenting
  • Pregnancy or breastfeeding
  • Contraindication to undergoing brain MRI per standard clinical practice guidelines
  • Vulnerable populations, including incarcerated inmates, dementia, and inability to provide consent

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Subjects with CADASIL treatment intervention

    Subjects with CADASIL placebo intervention

    Arm Description

    Subjects that have been diagnosed with both CADASIL and moderately to severely disabling migraine headaches will be treated with Fremanezumab injections.

    Subjects that have been diagnosed with both CADASIL and moderately to severely disabling migraine headaches will be treated with placebo injections.

    Outcomes

    Primary Outcome Measures

    Change in migraine-related disability
    Measured using the The Migraine Disability Assessment (MIDAS) questionnaire which is a brief, self-administered questionnaire designed to quantify headache-related disability over a 3 month period using number of days
    Change in headache intensity
    Measured using Headache Impact Test (HIT)-6 scores with the answers being never, rarely, sometimes, very often or always and equating to 6, 8, 10, 11, and 13 points respectively. Each answer is summated to equal the final score.
    Adverse events
    Number of adverse events reported

    Secondary Outcome Measures

    Full Information

    First Posted
    April 2, 2020
    Last Updated
    February 14, 2022
    Sponsor
    Mayo Clinic
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04334408
    Brief Title
    Safety and Efficacy of Fremanezumab for Migraine in Adult CADASIL
    Official Title
    A Phase II Double-Blinded Placebo Controlled Individual Subject Stepped Wedge Clinical Trial Evaluating the Safety and Efficacy of Fremanezumab for Migraine in Adult CADASIL
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2022
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Lack of funding to support the trial.
    Study Start Date
    December 2021 (Anticipated)
    Primary Completion Date
    December 2024 (Anticipated)
    Study Completion Date
    December 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Mayo Clinic

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Researchers are trying to find out more about the side effects of fremanezumab when treating patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) for migraine headaches.
    Detailed Description
    Subjects will receive 4 to 20 weeks of placebo injections followed by 12 weeks of monthly administered fremanezumab by subcutaneous injection (225 mg split four weeks apart for 12 weeks). Following completion of the 12 weeks of therapy, the participant will return to placebo for the washout period. Both the patient and the investigator will be blinded to the timing of transition to and from placebo and the transition to and from fremanezumab.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cadasil, Migraine

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Subjects with CADASIL treatment intervention
    Arm Type
    Active Comparator
    Arm Description
    Subjects that have been diagnosed with both CADASIL and moderately to severely disabling migraine headaches will be treated with Fremanezumab injections.
    Arm Title
    Subjects with CADASIL placebo intervention
    Arm Type
    Placebo Comparator
    Arm Description
    Subjects that have been diagnosed with both CADASIL and moderately to severely disabling migraine headaches will be treated with placebo injections.
    Intervention Type
    Drug
    Intervention Name(s)
    Fremanezumab
    Other Intervention Name(s)
    Ajovy
    Intervention Description
    Subjects will receive a single dose total 225 mg (1 injection of 225 mg per 1.5 mL injection) followed by a single dose of 225 mg (1 1.5mL injection) at four week intervals. Both the subject and the investigator will be blinded to the timing of transition to and from placebo and the transition to and from fremanezumab.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo injections during the run in and washout serves as the control condition. Both the subject and the investigator will be blinded to the timing of transition to and from placebo and the transition to and from fremanezumab.
    Primary Outcome Measure Information:
    Title
    Change in migraine-related disability
    Description
    Measured using the The Migraine Disability Assessment (MIDAS) questionnaire which is a brief, self-administered questionnaire designed to quantify headache-related disability over a 3 month period using number of days
    Time Frame
    Baseline, 2 week intervals up to 48 weeks
    Title
    Change in headache intensity
    Description
    Measured using Headache Impact Test (HIT)-6 scores with the answers being never, rarely, sometimes, very often or always and equating to 6, 8, 10, 11, and 13 points respectively. Each answer is summated to equal the final score.
    Time Frame
    Baseline, 2 week intervals up to 48 weeks
    Title
    Adverse events
    Description
    Number of adverse events reported
    Time Frame
    48 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria Age 18 to 70 years old English speaking Diagnosis of CADASIL confirmed by presence of a pathogenic NOTCH3 gene mutation Diagnosis of migraine for at least 12 months and diagnosis of chronic migraine for at least 28 days according to the International Classification of Headache Disorders MIDAS score of >10 points Ability to provide written informed consent Exclusion Criteria History of ischemic stroke within 4 weeks of screening assessment Screening blood pressure >150 mm Hg Use of onabotulinum toxin A 4 months prior to trial or other injectable/stimulatory/magnetic method of headache control Use of opiates or barbiturates 4 days prior to trial Patients with competing intracerebral pathology (e.g. history of intracerebral hemorrhage, multiple sclerosis) NYHA Class III or IV congestive heart failure History of myocardial infarction History of coronary bypass surgery or coronary stenting Pregnancy or breastfeeding Contraindication to undergoing brain MRI per standard clinical practice guidelines Vulnerable populations, including incarcerated inmates, dementia, and inability to provide consent
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    James F Meschia
    Organizational Affiliation
    Mayo Clinic
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Links:
    URL
    https://www.mayo.edu/research/clinical-trials
    Description
    Mayo Clinic Clinical Trials

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    Safety and Efficacy of Fremanezumab for Migraine in Adult CADASIL

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