Nortriptyline for Concussion

(PeCon Trial)

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Lancaster General Hospital

Disqualifiers: Neurological deficits, Seizure disorder, Psychiatric illness, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether nortriptyline can reduce headaches following a concussion. Participants will be divided into two groups: one will receive nortriptyline, and the other a placebo (a pill with no active medication). Researchers aim to determine if nortriptyline improves symptoms more quickly than the placebo over four weeks. Suitable candidates have experienced a concussion with persistent headaches for at least four weeks and are not currently taking other medications for their concussion, except for common pain relievers like ibuprofen or acetaminophen. As a Phase 4 trial, this research seeks to understand how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any medication for concussion other than NSAIDs or acetaminophen.

What is the safety track record for nortriptyline?

Research has shown that nortriptyline is usually well-tolerated by those needing help with headaches after a concussion. Studies have found that nortriptyline can improve symptoms and speed up the return to normal activities, such as attending school and playing sports. Although this medication is being tested for post-concussion headaches, its use in other conditions suggests it is safe. Always consult a healthcare professional about possible side effects before joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for concussions, which primarily focus on rest and symptom management with medications like acetaminophen or ibuprofen, nortriptyline offers a potentially novel approach. Nortriptyline is a tricyclic antidepressant, and researchers are interested in its ability to alleviate concussion symptoms by modulating neurotransmitters in the brain, which may help reduce headaches and improve mood disturbances often associated with concussions. This mechanism is different from typical pain relievers and could provide a more comprehensive treatment option for concussion symptoms, potentially leading to faster recovery and improved quality of life for patients.

What evidence suggests that nortriptyline might be an effective treatment for concussion?

Research has shown that nortriptyline can protect brain cells and reduce damage in conditions like certain types of strokes. This finding is promising because it suggests nortriptyline might also alleviate symptoms of brain injury, such as headaches after a concussion. Previous studies found that nortriptyline reduced the number of headaches by at least half for many people. Additionally, nortriptyline has fewer side effects than similar medications. In this trial, participants will receive either nortriptyline or a placebo to evaluate its effectiveness in reducing symptoms in people with headaches after a concussion. ^{1 2 3 6 7}

Who Is on the Research Team?

Patrick Moreno, MD

Principal Investigator

Lancaster General Health Sports Medicine

Laura DiPaolo, MD

Principal Investigator

Lancaster General Health Sports Medicine

Are You a Good Fit for This Trial?

This trial is for young people aged 13-21 who've had a concussion with headaches lasting over 4 weeks. They must be in good health, able to take pills, and not on other concussion meds except common painkillers. Those with severe brain injuries, uncontrolled mental illness, pregnancy, or known allergies to the drug can't join.

Inclusion Criteria

I am only taking NSAIDs or acetaminophen for my concussion.

It has been over 4 weeks since my concussion.

My headache, head pressure, and neck pain score is over 3.

Exclusion Criteria

You have any recent abnormal findings on a CT scan.

I have a history of Brugada syndrome.

I have specific nerve or brain function issues after an injury.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nortriptyline or placebo daily for 4 weeks, along with standard headache treatment

4 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nortriptyline
• Placebo

Trial Overview The study tests if Nortriptyline helps reduce headache symptoms faster than a placebo when added to standard treatments. Participants are randomly assigned to either the drug or placebo group and monitored weekly for symptom changes over four weeks.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

10mg capsule once daily for 4 weeks of nortriptyline

Group II: Control Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Lancaster General Hospital

Lead Sponsor

Trials

25

Recruited

4,100+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6802300/

Acute and preventive pharmacological treatment of post ... The primary outcome was a ≥ 50% reduction in headache frequency and whether prophylactic treatments were continued for 3 months after headache ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04226365

Study Details | NCT04226365 | Pediatric Concussion ... This is a randomized, placebo-controlled, double-blinded trial in which subjects with a post concussive headache meeting inclusion criterion will be ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2632945/

Nortriptyline Protects Mitochondria and Reduces Cerebral ... The present study demonstrates that nortriptyline is significantly neuroprotective in both cellular and animal models of cerebral ischemia.

4. withpower.com withpower.com/trial/phase-4-brain-injuries-traumatic-1-2020-4130a

Nortriptyline for Concussion · Info for Participants This trial tests whether nortriptyline can help people with headaches after a concussion. Participants will receive nortriptyline along with standard headache ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/65/NCT04226365/Prot_SAP_000.pdf

Treatment for post-concussive headache: A randomized, ... Nortriptyline has a superior side effect profile to that of other tricyclic antidepressants such as amitriptyline, but has never been studied ...

6. ccjm.org ccjm.org/content/84/8/623

Concussion: Evaluation and management In adults, we have clinically had success with nortriptyline 20 mg or gabapentin 300 mg at night as an initial prophylactic headache medication, ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2777144

Posttraumatic Headache Phenotype and Recovery Time ... The primary outcomes were time to recovery and concussion-attributable headache 3 months after injury; secondary outcome was headache 6 months ...