Clinical trial NCT04098250: Multidisciplinary Translational Approach to Investigate Mechanisms Predictors & Prevention of Persistent PTH
Official title: A Multidisciplinary Translational Approach to Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Post-Traumatic Headache
Keywords: headache
post-traumatic headache
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: University of Arizona
name: Translational Genomics Research Institute
name: Arizona State University
name: Phoenix VA Health Care System
name: United States Department of Defense
name: Amgen
First posted: 2019-09-23
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomization to erenumab or placebo
Primary purpose: PREVENTION

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.

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.

Eligibility 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 7-56 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 and an increase of at least 2 moderate to severe headache days compared to pre-TBI and at least a 30% increase
* 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
* Chronic headache (i.e., at least 15 headache days/month for more than 3 months) within 12 months prior to the mTBI that led to the current PTH, 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
* Started or changed dose of a headache preventive medication within the 3 months prior to screening
* Use of onabotulinumtoxinA in the head, neck or face region within 6 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

Primary outcomes:
measure: Moderate-to-severe headache day frequency
timeFrame: 9-12 weeks
Secondary outcomes:
measure: Responder rate
timeFrame: 9-12 weeks
measure: Chronic headache
timeFrame: 9-12 weeks
measure: Headache Impact Test (HIT-6)
timeFrame: 9-12 weeks
measure: Treatment day frequency
timeFrame: 9-12 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix VA Health Care System
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Todd Schwedt
role: PRINCIPAL_INVESTIGATOR
References: