Pediatric Concussion Outcomes

NCT04226365 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: 2019-83
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, placebo-controlled, double-blinded trial in which subjects with a post concussive headache meeting inclusion criterion will be assigned to one of two treatment groups: placebo or nortriptyline. Each group will be evaluated at week 0 and again each week for the next 4 weeks of treatment with a concussion survey that rates their symptoms. At the end of 4 weeks the study will be unblinded. It is hypothesized that the addition of nortriptyline to the standard headache treatments will result in more rapid decrease of symptom score than with placebo.

Conditions

Concussion Post Syndrome; Headaches Posttraumatic; Mild Traumatic Brain Injury

Keywords

concussion; headache; mild TBI; post concussion

Outcome Measures

Primary Outcomes (1)

• Post-Concussive Symptom Inventory (PSCI) Score

  Post-Concussive Symptom Inventory (PSCI) score of 0-1 on the headache symptom, where the score ranges from 0 (absent) to 6 (severe). A score of 0 is optimal, while a score of 6 is not optimal.

  4 weeks

Study Arms (2)

Experimental

EXPERIMENTAL

10mg capsule once daily for 4 weeks of nortriptyline

Drug: Nortriptyline

Control

PLACEBO COMPARATOR

10mg capsule once daily for 4 weeks of Thick-It filler

Drug: Placebo

Interventions

Nortriptyline DRUG

10mg capsule Nortryptyline

Also known as: Pamelor

Experimental

Placebo DRUG

10mg capsule Thick-It filler

Control

Eligibility Criteria

• Age: 13 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Participants aged 13-21 years old
• In good general health as evidenced by medical history and diagnosed with recent head trauma meeting ICHD-3 criteria for acute posttraumatic headache with symptom onset \< 7 days from trauma
• Ability to take oral medication and be willing to adhere to the medication regimen
• No loss of consciousness OR loss of consciousness \<30 minutes
• Headache symptoms persisting ≥4 weeks post trauma
• PCSHE score for headache + pressure in head + neck pain must be \> 3
• After week 4 post-concussion at time of enrollment
• Not currently receiving pharmacologic treatment for concussion asid from NSAIDs and acetaminophen

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Focal neurological deficits following injury
• Any acute abnormality on Computed Tomography (if obtained)
• History of known seizure disorder or moderate or severe TBI
• Current uncontrolled psychiatric illness given the potential side effects of the study drug (at investigator discretion).
• Current suicidal ideation as screened for on PHQ on intake
• A personal history of Brugada syndrome
• Known allergic reaction to nortriptyline
• Current pregnancy
• Positive COVID-19 test in prior 14 days

Sponsors & Collaborators

• Lancaster General Hospital: lead

Study Sites (1)

Penn Medicine Lancaster General Health

Lancaster, Pennsylvania, 17602, United States

Location

Related Publications (7)

• Choe MC, Blume HK. Pediatric Posttraumatic Headache: A Review. J Child Neurol. 2016 Jan;31(1):76-85. doi: 10.1177/0883073814568152. Epub 2015 Feb 10.

  PMID: 25670632 BACKGROUND

• Kacperski J, Hung R, Blume HK. Pediatric Posttraumatic Headache. Semin Pediatr Neurol. 2016 Feb;23(1):27-34. doi: 10.1016/j.spen.2015.08.005. Epub 2015 Aug 19.

  PMID: 27017019 BACKGROUND

• McCrory P, Meeuwisse W, Dvorak J, Aubry M, Bailes J, Broglio S, Cantu RC, Cassidy D, Echemendia RJ, Castellani RJ, Davis GA, Ellenbogen R, Emery C, Engebretsen L, Feddermann-Demont N, Giza CC, Guskiewicz KM, Herring S, Iverson GL, Johnston KM, Kissick J, Kutcher J, Leddy JJ, Maddocks D, Makdissi M, Manley GT, McCrea M, Meehan WP, Nagahiro S, Patricios J, Putukian M, Schneider KJ, Sills A, Tator CH, Turner M, Vos PE. Consensus statement on concussion in sport-the 5th international conference on concussion in sport held in Berlin, October 2016. Br J Sports Med. 2017 Jun;51(11):838-847. doi: 10.1136/bjsports-2017-097699. Epub 2017 Apr 26. No abstract available.

  PMID: 28446457 BACKGROUND

• Makdissi M, Schneider KJ, Feddermann-Demont N, Guskiewicz KM, Hinds S, Leddy JJ, McCrea M, Turner M, Johnston KM. Approach to investigation and treatment of persistent symptoms following sport-related concussion: a systematic review. Br J Sports Med. 2017 Jun;51(12):958-968. doi: 10.1136/bjsports-2016-097470. Epub 2017 May 8.

  PMID: 28483928 BACKGROUND

• Bernard CO, Ponsford JL, McKinlay A, McKenzie D, Krieser D. Do Concussive Symptoms Really Resolve in Young Children? J Head Trauma Rehabil. 2017 Nov/Dec;32(6):413-424. doi: 10.1097/HTR.0000000000000298.

  PMID: 28422893 BACKGROUND

• Kuczynski A, Crawford S, Bodell L, Dewey D, Barlow KM. Characteristics of post-traumatic headaches in children following mild traumatic brain injury and their response to treatment: a prospective cohort. Dev Med Child Neurol. 2013 Jul;55(7):636-41. doi: 10.1111/dmcn.12152. Epub 2013 Apr 5.

  PMID: 23560811 BACKGROUND

• Johnson JG, Harris ES, Spitzer RL, Williams JB. The patient health questionnaire for adolescents: validation of an instrument for the assessment of mental disorders among adolescent primary care patients. J Adolesc Health. 2002 Mar;30(3):196-204. doi: 10.1016/s1054-139x(01)00333-0.

  PMID: 11869927 BACKGROUND

Related Links

• Sport concussion assessment tool - 5th edition
• Pamelor \[package insert\]. Hazelwood, MO: Mallinckrodt Inc; 2019.

MeSH Terms

Conditions

Post-Concussion Syndrome; Post-Traumatic Headache; Brain Concussion; Headache

Interventions

Nortriptyline

Condition Hierarchy (Ancestors)

Head Injuries, Closed; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Wounds, Nonpenetrating; Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Brain Injuries, Traumatic; Brain Injuries; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Halle Becker, MPH, Research Project Manager
• Organization: Penn Medicine / Lancaster General Hospital

Halle.Becker@pennmedicine.upenn.edu

7175441777

Study Officials

• Patrick Moreno, MD

  Lancaster General Health Sports Medicine

  PRINCIPAL INVESTIGATOR

• Laura DiPaolo, MD

  Lancaster General Health Sports Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2020
• First Posted: January 13, 2020
• Study Start: February 15, 2020
• Primary Completion: May 31, 2023
• Study Completion: May 31, 2023
• Last Updated: September 10, 2025
• Results First Posted: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)