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

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests whether nortriptyline can help people with headaches after a concussion. Participants will receive nortriptyline along with standard headache treatments. The goal is to see if nortriptyline reduces headache symptoms faster by balancing brain chemicals. Nortriptyline has been tested previously for migraine prevention, but it was not effective when used alone.

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.

Is the drug nortriptyline effective for treating symptoms after a concussion?

Research shows that nortriptyline, a type of antidepressant, has been helpful for some people with conditions like tinnitus and depression, which suggests it might also help with concussion symptoms. However, its effectiveness specifically for concussion needs more direct study. ^{1 2 3 4 5}

Is nortriptyline generally safe for humans?

Nortriptyline has been studied in both adolescents and elderly people for depression, and while it did not show significant anticholinergic side effects (like dry mouth or blurred vision) in adolescents, it did affect memory performance in elderly individuals. A study on children and adolescents also looked at heart-related effects, but specific safety outcomes were not detailed in the provided abstracts. ^{5 6 7 8 9}

How does the drug nortriptyline differ from other treatments for concussion?

Nortriptyline is unique for concussion treatment as it is primarily a tricyclic antidepressant, typically used for depression and other conditions like tinnitus and Parkinson's disease-related depression. Its use in concussion is novel, as there are no standard treatments specifically targeting concussion symptoms with this mechanism of action. ^{2 5 6 10 11}

Research Team

Patrick Moreno, MD

Principal Investigator

Lancaster General Health Sports Medicine

Laura DiPaolo, MD

Principal Investigator

Lancaster General Health Sports Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Gabapentin and Tricyclics in the Treatment of Post-Concussive Headache, a Retrospective Cohort Study. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Antidepressant treatment of tinnitus patients: report of a randomized clinical trial and clinical prediction of benefit. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Use of Amitriptyline in the Treatment of Headache After Traumatic Brain Injury: Lessons Learned From a Clinical Trial. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of nortriptyline on memory self-assessment and performance in recovered elderly depressives. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Double-blind placebo-controlled study of nortriptyline in depressed adolescents using a "fixed plasma level" design. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

A retrospective study of serum levels and electrocardiographic effects of nortriptyline in children and adolescents. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Baseline and 2- to 3-year follow-up characteristics of placebo-washout responders from the nortriptyline study of depressed 6- to 12-year-olds. [2013]

9. England pubmed.ncbi.nlm.nih.gov

An investigation of the effects of lofepramine, nomifensine, amitriptyline and placebo on aspects of memory and psychomotor performance related to car driving. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

10-Hydroxynortriptyline and treatment effects in elderly depressed patients. [2013]

11. Denmark pubmed.ncbi.nlm.nih.gov

Anti-depressive treatment in Parkinson's disease. A controlled trial of the effect of nortriptyline in patients with Parkinson's disease treated with L-DOPA. [2022]