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

• ClinicalTrials.gov Identifier: NCT04098250
• Recruitment Status: Recruiting
• First Posted: September 23, 2019
• Last Update Posted: February 12, 2021
• Sponsor: Mayo Clinic
• 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

Study Description

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. These studies are described in more detail within a separate clinicaltrials.gov record.

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.

Study Design

• 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
• Actual Study Start Date: January 4, 2021
• Estimated Primary Completion Date: October 31, 2022
• Estimated Study Completion Date: August 31, 2023

Arms and Interventions

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

Outcome Measures

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).

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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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
• 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 (only an exclusion for patients participating in the brain MRI portion of this research):

  1. Metal implants
  2. Aneurysm clips
  3. Severe claustrophobia
  4. Implanted electronic device
  5. Insulin or infusion pump
  6. Cochlear/otologic/ear implant
  7. Non-removable prosthesis
  8. Implanted shunts/catheters
  9. Certain intrauterine devices
  10. Tattooed makeup
  11. Body piercings that cannot be removed
  12. Metal fragments
  13. Wire sutures or metal staples

• Factors that reduce MR image quality and interpretability (only an exclusion for patients participating in the brain MRI portion of this research):

  1. Dental braces or other non-removable devices (e.g., retainers)
  2. Prior brain surgery
  3. 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) (only an exclusion for patients participating in the neurophysiology studies)
• 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:

  1. At least 55 years of age with cessation of menses for 12 or more months; OR
  2. Younger than 55 years of age but no spontaneous menses for at least 2 years; OR
  3. 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
  4. Underwent bilateral oophorectomy; OR
  5. Underwent hysterectomy; OR
  6. 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

Contacts and Locations

Contacts

Contact: Teri Radam; 480-342-3775; Radam.Teri@Mayo.Edu

Locations

United States, Arizona

Phoenix VA Health Care System; Recruiting

Phoenix, Arizona, United States, 85012

Contact: Katherine Ross, PhD 602-277-5551 ext 7982 Katherine.Ross3@va.gov

Mayo Clinic; 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; 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

• Principal Investigator: Todd Schwedt; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Todd J. Schwedt, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT04098250
• Other Study ID Numbers: 19-003200
• First Posted: September 23, 2019
• Last Update Posted: February 12, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Post-Traumatic Headache; Headache; Pain; Neurologic Manifestations; Headache Disorders, Secondary; Headache Disorders; 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