Treatment of Acute PTH With a CGRP Receptor mAb in Military Service Members and Civilians With mTBI

• ClinicalTrials.gov Identifier: NCT05049057
• Recruitment Status: Recruiting
• First Posted: September 17, 2021
• Last Update Posted: September 30, 2022
• Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
• Information provided by (Responsible Party): Henry M. Jackson Foundation for the Advancement of Military Medicine

Study Description

Brief Summary:

This study aims to assess the effect and safety of erenumab compared to placebo for the treatment of acute posttraumatic headache (PTH) in military service members and civilians with mild traumatic brain injury (mTBI).

Condition or disease	Intervention/treatment	Phase
Posttraumatic Headache; Mild Traumatic Brain Injury	Drug: Erenumab 140 Mg/mL Subcutaneous Solution; Drug: Placebo	Phase 2

Detailed Description:

Headache is recognized as one of the most common and disabling symptoms following head trauma. This study is designed to assess a calcitonin gene-related peptide (cGRP) monoclonal antibody (erenumab) for the preventive treatment of PTH based on the rationale that headache posttrauma is similar to migraine and is mediated by the activation of the trigeminal vascular system and subsequent release of cGRP. This study is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and efficacy of erenumab 140 mg for the treatment of PTH in military service members and civilians with mTBI at military treatment facilities across the United States.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 404 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment of Acute Post-Traumatic Headache With Erenumab 140 mg, Military Service Members and Civilians With Mild TBI: A Randomized, Double Blind, Placebo Controlled, Multicenter 12-week Duration Study Followed by a 4-week Open-Label Safety Extension
• Actual Study Start Date: July 19, 2022
• Estimated Primary Completion Date: May 19, 2026
• Estimated Study Completion Date: May 19, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active Drug; Erenumab administered once monthly via two 70-mg subcutaneous injections at 3 time points over a 12-week period.	Drug: Erenumab 140 Mg/mL Subcutaneous Solution; Active erenumab delivered via subcutaneous injection.; Other Name: Aimovig
Placebo Comparator: Placebo; Placebo administered once monthly via two subcutaneous injections at 3 time points over a 12-week period.	Drug: Placebo; Placebo delivered via subcutaneous injection.

Outcome Measures

Primary Outcome Measures :

1. Monthly Headache Days [ Time Frame: Week 8 to Week 12 ]
   Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary

Secondary Outcome Measures :

1. Monthly Headache Days [ Time Frame: Week 0 to Week 12 ]
   Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary
2. Monthly Headache Days [ Time Frame: Week 0 to Week 4 ]
   Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary
3. Monthly Headache Days [ Time Frame: Week 0 to Week 8 ]
   Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary
4. Adverse Events [ Time Frame: Week 0 to Week 12 ]
   Number of adverse events reported in erenumab group compared to placebo
5. Return to Full Duty [ Time Frame: Week 0 to Week 12 ]
   Time to return to full activity as measured by the daily headache diary
6. Concomitant Medications [ Time Frame: Week 0 to Week 12 ]
   Monthly use of medications for acute headache treatment
7. Headache Days [ Time Frame: Week 0 to Week 12 ]
   Monthly headache days after early acute versus late acute administration of erenumab compared to placebo
8. HPFID Activity [ Time Frame: Week 0 to Week 12 ]
   Monthly impact on everyday activity scores as measured by the Headache Physical Function Impact Diary Domain 1
9. HPFID Physical Impairment [ Time Frame: Week 0 to Week 12 ]
   Monthly impact on physical impairment scores as measured by the Headache Physical Function Impact Diary Domain 2
10. HIT-6 [ Time Frame: Week 0 to Week 12 ]
    Change from baseline in headache impact scores as measured by the Headache Impact Test
11. PHQ-9 [ Time Frame: Week 0 to Week 12 ]
    Change from baseline in depressive symptoms after mTBI as measured by the self-report questionnaire, Patient Health Questionnaire-9, Total Score. Total scores range from a minimum of 0 to a maximum of 27, which are rated from minimal to severe levels of depression.
12. ISI [ Time Frame: Week 0 to Week 12 ]
    Change from baseline in insomnia scores as measured by the Insomnia Severity Index

Other Outcome Measures:

1. MSQ [ Time Frame: Week 0 to Week 12 ]
   Change from baseline in quality of life scores as measured by the Migraine-specific Quality of Life Questionnaire
2. ASC-12 [ Time Frame: Week 0 to Week 12 ]
   Change from baseline in frequency of allodynia symptoms as measured by the Allodynia Symptom Checklist
3. ANAM [ Time Frame: Week 0 to Week 12 ]
   Change from baseline in neuropsychological functions as assessed by the Automated Neuropsychological Assessment Metrics
4. Function of Time [ Time Frame: 0-24 hours, 24-72 hours, 72-144 hours ]
   Effect of erenumab compared to placebo as a function of time from mTBI to first dose of erenumab as measured by the daily headache diary

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female ≥18 and ≤50 years of age
• mTBI from any cause including impact, rotational acceleration, blast, or a combination, has occurred within the prior 7 days
• PTH has occurred within the prior 7 days
• Able to provide informed consent
• Likely to stay in the same geographical area for the duration of study
• Has a personal health care provider for standard of care PTH and TBI, including education, diagnostic procedures including neuroimaging and treatment, as deemed clinically indicated by the health care provider

Exclusion Criteria:

• Sustained a moderate or severe TBI, rather than mTBI, indicated with at least 1 of the following associated with head injury:

  1. abnormal structural imaging
  2. loss of consciousness for >30 minutes
  3. alteration of consciousness/mental state for >24 hours 3. post-traumatic amnesia for >1 day
• Participants with ongoing chronic migraine or other chronic daily headache disorders at the time of injury

Contacts and Locations

Contacts

Contact: Annabel Lee Raboy; 301-461-1067; annabellee.raboy.ctr@usuhs.edu

Contact: Molly Malarkey; molly.malarkey.ctr@usuhs.edu

Locations

United States, North Carolina

Womack Army Medical Center - Fort Bragg; Recruiting

Fort Bragg, North Carolina, United States, 28310

Contact: Calley Smith 240-653-6725 calley.c.smith.ctr@mail.mil

Principal Investigator: CAPT Scott Klimp

Naval Medical Center Camp Lejeune; Recruiting

Jacksonville, North Carolina, United States, 28547

Contact: Heather Hill 910-450-3768 heather.hill.ctr@usuhs.edu

Principal Investigator: CAPT Diana Fu

United States, Texas

Brooke Army Medical Center - Fort Sam Houston; Recruiting

Fort Sam Houston, Texas, United States, 78234

Contact: Amy Guthrie 210-275-8108 amy.e.guthrie.ctr@mail.mil

Principal Investigator: Maj Tyler Davis

Sponsors and Collaborators

Henry M. Jackson Foundation for the Advancement of Military Medicine

Investigators

• Principal Investigator: David L Brody, MD, PhD; Uniformed Services University of the Health Sciences

More Information

• Responsible Party: Henry M. Jackson Foundation for the Advancement of Military Medicine
• ClinicalTrials.gov Identifier: NCT05049057
• Other Study ID Numbers: CNRM-CGRP-2020
• First Posted: September 17, 2021
• Last Update Posted: September 30, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Identifier-free participant data sets will be shared with the Uniformed Services University Center for Neuroscience and Regenerative Medicine Data Repository. Identifier-free data sets may also be shared with the Federal Interagency Traumatic Brain Injury Research (FITBIR) Data Repository
• Time Frame: After study completion, data sets will be de-identified and shared with the repositories. De-identified data sets will be stored in the repositories indefinitely.

Access Criteria

Access to the CNRM Data Repository will be determined b the CNRM Data Quality, Access, and Publication Committee. Investigators requesting access to the data will provide a list of investigators and collaborators who will have access to the data, documentation of Ethical Conduct of Research and Human Participants Protection Training, and documentation of Institutional Review Board Approval of the research project.

Access to FITBIR will follow FITBIR Access Criteria.

• URL: http://fitbir.nih.gov/content/access-data

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Post-Traumatic Headache; Headache; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Pain; Neurologic Manifestations; Head Injuries, Closed; Wounds, Nonpenetrating; Headache Disorders, Secondary; Headache Disorders; Erenumab; Calcitonin Gene-Related Peptide Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs