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Multidisciplinary Translational Approach to Investigate Mechanisms Predictors & Prevention of Persistent PTH

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04098250
Recruitment Status : Not yet recruiting
First Posted : September 23, 2019
Last Update Posted : October 18, 2019
Sponsor:
Collaborators:
University of Arizona
Translational Genomics Research Institute
Arizona State University
Phoenix VA Health Care System
United States Department of Defense
Amgen
Information provided by (Responsible Party):
Todd J. Schwedt, Mayo Clinic

Brief Summary:

This is a United States Department of Defense funded Focused Program study that aims to identify mechanisms and predictors for persistent of post-traumatic headache attributed to mild traumatic brain injury, and identify methods of preventing post-traumatic headache persistence.

The objective of the clinical trial component of the Focused Program is to determine whether intervention with erenumab is an effective treatment for PTH attributed to mTBI.


Condition or disease Intervention/treatment Phase
Post-Traumatic Headache Drug: Erenumab Other: Placebo Phase 2

Detailed Description:

The human studies component of this Focused Program includes clinical phenotyping, neurophysiology, molecular and genetic biomarker discovery, brain imaging, and a clinical trial.These data will be utilized to characterize post-traumatic headache and build univariate and multivariate predictive models for post-traumatic headache persistence and for the response to post-traumatic headache treatment.

The clinical trial is a double-blind, randomized, placebo-controlled investigation of erenumab for the treatment of post-traumatic headache. Participants will be randomized when PTH has been present for 35-56 days. Follow-up questionnaires, headache diary data, pain threshold results, and brain imaging data will be collected longitudinally during the clinical trial to assess for changes over time and associations of such changes with post-traumatic headache treatment outcomes.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 1:1 randomization to erenumab or placebo
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: A Multidisciplinary Translational Approach to Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache
Estimated Study Start Date : December 20, 2019
Estimated Primary Completion Date : October 31, 2022
Estimated Study Completion Date : August 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Headache

Arm Intervention/treatment
Experimental: Erenumab
140 mg erenumab
Drug: Erenumab
a CGRP receptor monoclonal antibody
Other Name: Aimovig

Placebo Comparator: Placebo
placebo comparator
Other: Placebo
Placebo




Primary Outcome Measures :
  1. Moderate-to-severe headache day frequency [ Time Frame: 9-12 weeks ]
    Moderate-to-severe headache day frequency measured at weeks 9-12 after administration of first dose of erenumab 140mg or placebo vs. frequency of moderate-to-severe headache days during the 4-week baseline phase (BP). A moderate-to-severe headache day is defined as any headache lasting at least 2 hours and which at any point reaches at least moderate intensity.


Secondary Outcome Measures :
  1. Responder rate [ Time Frame: 9-12 weeks ]
    Percentage of patients with at least a 50% reduction in headache days during weeks 9-12 after administration of first dose of erenumab 140 mg or placebo compared to baseline phase.

  2. Chronic headache [ Time Frame: 9-12 weeks ]
    Percentage of patients with chronic headache, defined as at least 15 headache days, during weeks 9-12 after administration of first dose of erenumab 140 mg or placebo compared to baseline phase.

  3. Headache Impact Test (HIT-6) [ Time Frame: 9-12 weeks ]
    Headache Impact Test (HIT-6) score at weeks 9-12 after administration of first dose of erenumab 140 mg or placebo compared to baseline phase.

  4. Treatment day frequency [ Time Frame: 9-12 weeks ]
    Acute treatment day frequency measured at weeks 9-12 after administration of first dose of erenumab 140mg or placebo compared to baseline phase. Acute treatment day is any day on which analgesic, triptan, or ergotamine containing medication is taken, or device neuromodulation [e.g. vagal or trigeminal nerve electrical stimulation or single pulse transcranial magnetic stimulation] is administered to relieve headache.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

PATH A (all studies including the clinical trial)

Inclusion Criteria:

  • Have a diagnosis of acute PTH attributed to mild traumatic injury to the head as defined by the International Classification of Headache Disorders (ICHD-3).
  • PTH onset 7-28 days prior to the time of enrollment.
  • Adults 18-70 years of age.
  • Willing to be randomized to either of the two clinical trial treatment arms.
  • Willing to maintain a headache diary.
  • Willing and able to return for follow-up visits.

Additional Inclusion Criteria for Randomization into the Clinical Trial (assessed after run-in phase):

  • 5 or more moderate or severe headache days during the 4-week run-in phase.
  • At least 80% compliant with diary keeping during the 4-week run-in phase (i.e., provides data on at least 80% of days).

Exclusion Criteria:

  • Episodic tension-type headache, migraine, or other headaches with at least 4 headache days/month on average over the 6 months prior to the mTBI resulting in PTH.
  • Previous history of chronic headache (i.e., at least 15 headache days/month) including PPTH, chronic migraine, medication overuse headache, new daily persistent headache, hemicrania continua, chronic tension-type headache.
  • Diminished decision-making capacity that in the investigator's opinion would interfere with the person's ability to provide informed consent and complete study procedures.
  • Current or prior use of preventive medications for migraine or other primary headache disorder.
  • Use of onabotulinumtoxinA in the head, neck or face region within 12 months of screening.
  • During the 6 months before screening, use of opioids or barbiturates on an average of at least 4 days per month.
  • Subjects who underwent an intervention or used a device (e.g., nerve blocks, transcranial magnetic stimulation, vagal nerve stimulation, or electrical trigeminal nerve stimulation) for headache.
  • History of major psychiatric disorder such as schizophrenia and bipolar disorder.
  • History or evidence of any unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
  • History of positive neuroimaging findings that indicate a moderate or severe TBI.
  • Contraindications to magnetic resonance imaging, including, but not limited to: ◦Metal implants;

    • Aneurysm clips;
    • Severe claustrophobia;
    • Implanted electronic devices;
    • Insulin or infusion pump;
    • Cochlear/otologic/ear implant;
    • Non-removable prosthesis;
    • Implanted shunts/catheters;
    • Certain intrauterine devices;
    • Tattooed makeup;
    • Body piercings that cannot be removed;
    • Metal fragments;
    • Wire sutures or metal staples.
  • Factors that reduce MR image quality and interpretability:

    • Dental braces or other non-removable devices (e.g., retainers);
    • Prior brain surgery;
    • Known brain MRI abnormality that in the investigator's opinion will significantly impact MRI data.
  • Sensory disorders that in the investigator's opinion might affect perception of cutaneous thermal stimuli (e.g., peripheral neuropathy).
  • Pregnancy.
  • Breastfeeding.
  • History of myocardial infarction, stroke, transient ischemic attack, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months prior to screening.
  • Not willing to use a reliable form of contraception (for women of childbearing potential) through 16 weeks after the last dose of erenumab. Acceptable methods of birth control include not having intercourse, hormonal birth control methods, intrauterine devices, surgical contraceptive methods, or two barrier methods (each partner must use a barrier method) with spermicide. A reliable form of contraception must be started prior to or at the time of starting the run-in phase. Not being of childbearing potential is defined as any woman who: ◦Is post-menopausal by history, defined as: ◾At least 55 years of age with cessation of menses for 12 or more months; OR

    • Younger than 55 years of age but no spontaneous menses for at least 2 years; OR
    • Younger than 55 years of age and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy), AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels at least 40 IU/L) or postmenopausal estradiol level (less than 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved;
    • OR

      • Underwent bilateral oophorectomy; OR
      • Underwent hysterectomy; OR
      • Underwent bilateral salpingectomy.
  • Currently or within 90 days prior to screening: received treatment in another drug study or an investigational device study.
  • Has previously received any CGRP ligand or receptor targeted monoclonal antibody.

PATH B (all studies except for the clinical trial)

Inclusion Criteria:

  • Have a diagnosis of acute PTH attributed to mild traumatic injury to the head as defined by the International Classification of Headache Disorders (ICHD-3).
  • PTH onset 7-28 days prior to the time of enrollment.
  • Adults 18-70 years of age.
  • Willing to maintain a headache diary.
  • Willing and able to return for follow-up visits.

Exclusion Criteria:

  • Episodic tension-type headache, migraine, or other headaches with at least 4 headache days/month on average over the 6 months prior to the mTBI resulting in PTH.
  • Previous history of chronic headache (i.e. at least 15 headache days/month) including PPTH, chronic migraine, medication overuse headache, new daily persistent headache, hemicrania continua, chronic tension-type headache.
  • Diminished decision-making capacity that in the investigator's opinion would interfere with the person's ability to provide informed consent and complete study procedures.
  • Current or prior use of preventive medications for migraine or other primary headache disorder.
  • Use of onabotulinumtoxinA in the head, neck or face region within 12 months of screening.
  • During the 6 months before screening, use of opioids or barbiturates on at least 4 days per month.
  • Subjects who underwent an intervention or used a device (e.g., nerve blocks, transcranial magnetic stimulation, vagal nerve stimulation, or electrical trigeminal nerve stimulation) for headache.
  • History of major psychiatric disorder such as schizophrenia and bipolar disorder.
  • History or evidence of any unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
  • History of positive neuroimaging findings that indicate a moderate or severe TBI.
  • Contraindications to magnetic resonance imaging, including, but not limited to: ◦Metal implants;

    • Aneurysm clips;
    • Severe claustrophobia;
    • Implanted electronic devices;
    • Insulin or infusion pump;
    • Cochlear/otologic/ear implant;
    • Non-removable prosthesis;
    • Implanted shunts/catheters;
    • Certain intrauterine devices;
    • Tattooed makeup;
    • Body piercings that cannot be removed;
    • Metal fragments;
    • Wire sutures or metal staples.
  • Factors that reduce MR image quality and interpretability:

    • Dental braces or other non-removable devices (e.g., retainers);
    • Prior brain surgery;
    • Known brain MRI abnormality that in the investigator's opinion will significantly impact MRI data.
  • Sensory disorders that in the investigator's opinion might affect perception of cutaneous thermal stimuli (e.g., peripheral neuropathy).
  • Pregnancy.
  • Breastfeeding.
  • Currently or within 90 days prior to screening: received treatment in another drug study or an investigational device study.

PATH C (phenotyping, molecular/genetic biomarker, clinical trial)

Inclusion Criteria:

  • Have a diagnosis of acute PTH attributed to mild traumatic injury to the head as defined by the International Classification of Headache Disorders (ICHD-3).
  • PTH onset 7-28 days prior to the time of enrollment.
  • Adults 18-70 years of age.
  • Willing to be randomized to either of the two clinical trial treatment arms.
  • Willing to maintain a headache diary.
  • Willing and able to return for follow-up visits.

Additional Inclusion Criteria for randomization into the Clinical Trial (assessed after run-in phase):

  • 5 or more moderate or severe headache days during the 4-week run-in phase.
  • At least 80% compliant with diary keeping during the 4-week run-in phase (i.e., provides data on at least 80% of days).

Exclusion Criteria:

  • Episodic tension-type headache, migraine, or other headaches with at least 4 headache days/month on average over the 6 months prior to the mTBI resulting in PTH.
  • Previous history of chronic headache (i.e. at least 15 headache days/month) including PPTH, chronic migraine, medication overuse headache, new daily persistent headache, hemicrania continua, chronic tension-type headache.
  • Diminished decision-making capacity that in the investigator's opinion would interfere with the person's ability to provide informed consent and complete study procedures.
  • Current or prior use of preventive medications for migraine or other primary headache disorder.
  • Use of onabotulinumtoxinA in the head, neck or face region within 12 months of screening.
  • During the 6 months before screening, use of opioids or barbiturates on average at least 4 days per month.
  • Subjects who underwent an intervention or used a device (e.g., nerve blocks, transcranial magnetic stimulation, vagal nerve stimulation, or electrical trigeminal nerve stimulation) for headache.
  • History of major psychiatric disorder such as schizophrenia and bipolar disorder.
  • History or evidence of any unstable or clinically significant medical condition that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
  • Pregnancy.
  • Breastfeeding.
  • History of myocardial infarction, stroke, transient ischemic attack, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months prior to screening.
  • Not willing to use a reliable form of contraception (for women of childbearing potential) through 16 weeks after the last dose of erenumab. Acceptable methods of birth control include not having intercourse, hormonal birth control methods, intrauterine devices, surgical contraceptive methods, or two barrier methods (each partner must use a barrier method) with spermicide. A reliable form of contraception must be started prior to or at the time of starting the run-in phase. Not being of childbearing potential is defined as any woman who: ◦Is post-menopausal by history, defined as: ◾At least 55 years of age with cessation of menses for 12 or more months; OR

    • Younger than 55 years of age but no spontaneous menses for at least 2 years; OR
    • Younger than 55 years of age and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy), AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels at least 40 IU/L) or postmenopausal estradiol level (less than 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved;
    • OR

      • Underwent bilateral oophorectomy; OR
      • Underwent hysterectomy; OR
      • Underwent bilateral salpingectomy.
  • Currently or within 90 days prior to screening: received treatment in another drug study or an investigational device study.
  • Has previously received any CGRP ligand or receptor targeted monoclonal antibody.

PARTICIPANT ELIGIBILITY CRITERIA FOR HEALTHY CONTROLS (Healthy Controls do not participate in the clinical trial)

Inclusion Criteria:

  • Adults 18-70 years of age.
  • Willing and able to return for follow-up visits.

Exclusion Criteria:

  • History of traumatic brain injury.
  • History of migraine or other headaches.

    ◦Tension-type headache up to an average of 3 days per month is allowed.

  • Diminished decision-making capacity that in the investigator's opinion would interfere with the person's ability to provide informed consent and complete study procedures.
  • During the 6 months before screening, use of opioids or barbiturates on an average of at least 4 days per month.
  • History of major psychiatric disorder such as schizophrenia and bipolar disorder.
  • History or evidence of any unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
  • Contraindications to magnetic resonance imaging, including, but not limited to: ◦Metal implants;

    • Aneurysm clips;
    • Severe claustrophobia;
    • Implanted electronic devices;
    • Insulin or infusion pump;
    • Cochlear/otologic/ear implant;
    • Non-removable prosthesis;
    • Implanted shunts/catheters;
    • Certain intrauterine devices;
    • Tattooed makeup;
    • Body piercings that cannot be removed;
    • Metal fragments;
    • Wire sutures or metal staples.
  • Factors that reduce MR image quality and interpretability:

    • Dental braces or other non-removable devices (e.g., retainers);
    • Prior brain surgery;
  • Known brain MRI abnormality that in the investigator's opinion will significantly impact MRI data.
  • Sensory disorders that in the investigator's opinion might affect perception of cutaneous thermal stimuli (e.g., peripheral neuropathy).
  • Pregnancy.
  • Breastfeeding.
  • Currently or within 90 days prior to screening: received treatment in another drug study or an investigational device study.
  • Has previously received any CGRP ligand or receptor targeted monoclonal antibody.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04098250


Contacts
Layout table for location contacts
Contact: Teri Radam 480-342-3775 Radam.Teri@Mayo.Edu

Locations
Layout table for location information
United States, Arizona
Phoenix VA Health Care System Not yet recruiting
Phoenix, Arizona, United States, 85012
Contact: Katherine Ross, PhD    602-277-5551 ext 7982    Katherine.Ross3@va.gov   
Mayo Clinic Not yet recruiting
Phoenix, Arizona, United States, 85054
Contact: Teri Radam, CCRP    480-342-3775    Radam.Teri@Mayo.Edu   
Principal Investigator: Todd Schwedt, MD         
Mayo Clinic in Arizona Not yet recruiting
Scottsdale, Arizona, United States, 85259
Contact: Teri Radam, CCRP    480-342-3775    Radam.Teri@Mayo.Edu   
Principal Investigator: Todd Schwedt, MD         
Sponsors and Collaborators
Mayo Clinic
University of Arizona
Translational Genomics Research Institute
Arizona State University
Phoenix VA Health Care System
United States Department of Defense
Amgen
Investigators
Layout table for investigator information
Principal Investigator: Todd Schwedt Mayo Clinic

Additional Information:
Layout table for additonal information
Responsible Party: Todd J. Schwedt, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT04098250     History of Changes
Other Study ID Numbers: 19-003200
First Posted: September 23, 2019    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Todd J. Schwedt, Mayo Clinic:
headache
post-traumatic headache
Additional relevant MeSH terms:
Layout table for MeSH terms
Post-Traumatic Headache
Headache
Headache Disorders, Secondary
Headache Disorders
Pain
Neurologic Manifestations
Signs and Symptoms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Erenumab
Calcitonin Gene-Related Peptide Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs