Concussion Post SyndromePhase 4PeConNCT04226365
Pediatric Concussion Outcomes
A Phase 4 study testing Nortriptyline in people with Concussion Post Syndrome and Headaches Posttraumatic, run by Lancaster General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 21 yearsHealthy volunteers can take part
- Conditions the study is for
- Concussion Post Syndrome, Headaches Posttraumatic, Mild Traumatic Brain Injury
- What is being tested?
- Nortriptyline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2020to 31 May 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 21 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 10Show fewer
- A personal history of Brugada syndrome
- Known allergic reaction to nortriptyline
- Current pregnancy
- Positive COVID-19 test in prior 14 days
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn Medicine Lancaster General Health
Lancaster, Pennsylvania, 17602
About this study
Official title: Treatment for Post-concussive Headache: A Randomized, Placebo-controlled, Double Blinded Trial
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.
Read the detailed description
Participants are randomly assigned to one of two treatment groups. The experimental group receives standard headache treatment including Tylenol, NSAIDs 2-3x/week, vestibular PT and daily nortriptyline 10mg oral. The control group also receives the standard headache treatment, but will instead be given a placebo, which will look physically identical to the nortriptyline capsule and be comprised of non-active pharmaceutical grade excipient.
- Being tested
- Nortriptyline, Placebo
- Keywords
- concussion, headache, mild TBI, post concussion
- Medical subject headings
- Post-Concussion Syndrome, Post-Traumatic Headache, Brain Concussion, Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NortriptylineDrug
Also called Pamelor
10mg capsule Nortryptyline
PlaceboDrug
10mg capsule Thick-It filler
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | 10mg capsule once daily for 4 weeks of nortriptyline Receives: Drug: Nortriptyline |
| Control | Placebo comparator | 10mg capsule once daily for 4 weeks of Thick-It filler Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start15 Feb 2020
- Primary completion31 May 2023
- Study completion31 May 2023
Why it stopped: The study was stopped prematurely due to a low enrollment rate.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Concussion Post SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lancaster General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Patrick Moreno, MD, Principal investigator, Lancaster General Health Sports MedicineLaura DiPaolo, MD, Principal investigator, Lancaster General Health Sports Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04226365
- Sponsor's protocol ID
- 2019-83
- Acronym
- PeCon
- Status last verified
- Sep 2025
- First submitted
- 9 Jan 2020
- Last updated
- 10 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25670632Kacperski 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.
PubMed 27017019McCrory 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.
PubMed 28446457Makdissi 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.
PubMed 28483928Bernard 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.
PubMed 28422893Kuczynski 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.
PubMed 23560811Johnson 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.
PubMed 11869927
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment for Post-concussive Headache: A Randomized, Placebo-controlled, Double Blinded Trial
- ClinicalTrials.gov ID
- NCT04226365
- Acronym / sponsor ID
- PeCon / 2019-83
- Keywords
- concussion, headache, mild TBI, post concussion
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped prematurely due to a low enrollment rate.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Lancaster General HospitalUniversity, hospital or other
- Study start
- 15 Feb 2020 (actual)
- Primary completion
- 31 May 2023 (actual)
- Study completion
- 31 May 2023 (actual)
- First posted
- 13 Jan 2020 (actual)
- Results
- Posted 10 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Participants are randomly assigned to one of two treatment groups. The experimental group receives standard headache treatment including Tylenol, NSAIDs 2-3x/week, vestibular PT and daily nortriptyline 10mg oral. The control group also receives the standard headache treatment, but will instead be given a placebo, which will look physically identical to the nortriptyline capsule and be comprised of non-active pharmaceutical grade excipient.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Nortriptyline10mg capsule once daily for 4 weeks of nortriptyline |
| Control | Placebo comparator | Drug: Placebo10mg capsule once daily for 4 weeks of Thick-It filler |
Who may qualify
- Ages
- 13 to 21 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NortriptylineAlso: Pamelor10mg capsule Nortryptyline | Drug | Experimental |
| Placebo10mg capsule Thick-It filler | Drug | Control |
Primary outcome
Post-Concussive Symptom Inventory (PSCI) Score
Time frame: 4 weeks
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25670632Choe 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.
- Background: PubMed 27017019Kacperski 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.
- Background: PubMed 28446457McCrory 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.
- Background: PubMed 28483928Makdissi 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.
- Background: PubMed 28422893Bernard 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.
- Background: PubMed 23560811Kuczynski 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.
- Background: PubMed 11869927Johnson 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.
- Sport concussion assessment tool - 5th editionLink provided by the sponsor.
- Pamelor \[package insert\]. Hazelwood, MO: Mallinckrodt Inc; 2019.Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Concussion Post Syndrome
Not yet recruiting
Electroencephalography Markers of Brain Stimulation in Post-Concussion Patients
Patients With Persistent Post-concussion Symptoms
Not yet recruitingObservational study
Cognitive Effects of Hyperbaric Oxygen Therapy (HBOT) After a Traumatic Brain Injury
Traumatic Brain Injury, Post-Concussion Syndrome
Recruiting
Percutaneous Electrical Nerve Field Stimulation (PENFS) in Patients With Post Concussion Syndrome (PCS)
Post-Concussion Syndrome, COVID Long-Haul
Recruiting
Control Network Neuromodulation to Enhance Cognitive Training in Complex Traumatic Brain Injury
Traumatic Brain Injury
Active, not recruiting
Move&Connect: A Program for Youth With Concussion and Their Caregivers.
Post-Concussion Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Moreno, MD principal investigator
Lancaster General Health Sports Medicine
Laura DiPaolo, MD principal investigator
Lancaster General Health Sports Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nortriptyline in people with Concussion Post Syndrome and Headaches Posttraumatic, run by Lancaster General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Post-Concussive Symptom Inventory (PSCI) Score (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04226365, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2025.