Naratriptan for the Treatment of Post Traumatic Headache Associated With Cognitive Dysfunction

Condition(s) targeted: Post Traumatic Headache

Intervention: naratriptan HCl (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Cady, Roger, M.D.

Official(s) and/or principal investigator(s):
Roger K Cady, MD, Principal Investigator, Affiliation: Clinvest

The purpose of this study is to determine whether naratriptan, a medication approved for treatment of migraine, is effective in the treatment of post traumatic headache associated with cognitive dysfunction.

Official title: Evaluation of the Efficacy of Naratriptan for the Treatment and Prevention of Post Traumatic Headache Associated With Cognitive Dysfunction

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome:

Number of headache days as measured by the Headache Diary

Impact of headache symptoms as measured by the HIT-6 questionnaire

Cognitive function as measured by Mental Efficiency Workload Test (MEWT)

Secondary outcome:

Subject satisfaction with therapy as measured by Satisfaction with Medication questionnaire

Quality of life as measured by Headache Specific Quality of Life questionnaire (MSQ)

Sustained treatment effect as measured by the MEWT and Headache Diary

Detailed description: Naratriptan has demonstrated efficacy in relieving headache. Other studies have demonstrated that primary headaches with at least one headache feature are likely to respond to triptans. In addition, there are anecdotal reports of triptans being effective in post traumatic headaches, especially if headache features are noted in the patient's history. Further, there are several small pilot studies with triptans demonstrating a prompt improvement in headache-induced cognitive changes. Cognitive performance can be measured by the Mental Efficiency Workload Test (MEWT), a handheld Palm neuropsychological test battery that measures mental efficiency. This tool can be used to demonstrate short and long term improvement in mental status beyond that seen at baseline.

Informal observations by the protocol authors have suggested that the use of triptans on a routine basis may ameliorate the headache and associated symptomatology of post traumatic headache. Therefore, this study is undertaken to study the use of naratriptan in the treatment of post traumatic headache. Roger K. Cady, MD, serves as the sponsor. The study is funded by GlaxoSmithKline.

56 subjects with a formal diagnosis of Chronic post-traumatic headache attributed to mild head injury (IHS/ICHD-II 5. 2.2) and with self-reported mild cognitive inefficiency secondary to headache will be enrolled at two sites in the U. S. (Headache Care Center/Clinvest, Springfield, MO and National Rehabilitation Hospital, Washington, D. C.). Subjects meeting inclusion criteria will complete a physical examination and baseline testing and be randomized 1: 1 to naratriptan 2. 5mg bid x 30 days or a matched placebo bid x 30 days. A daily diary will document response to treatment. Subjects will return to the clinic at Day 10 and Day 30 and complete phone contacts at Days 5, 15, 21, 32 and 90. Information will be collected throughout the study on questionnaires related to headache impact, general health, satisfaction with medication, and quality of life. Cognition will be measured using the MEWT.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Males and females between the ages of 18-55. A female is eligible to enter and

participate if she is of: non-childbearing potential (i. e., physiologically incapable of becoming pregnant); or, child-bearing potential, has a negative pregnancy test (urine or serum) at screen, and agrees to one of the following: Complete abstinence from intercourse from 2 weeks prior to administration of the investigational product, throughout the study, and for a time interval (5 days) after completion or premature discontinuation from the study; subjects utilizing this method must agree to use alternate method of contraception if they become sexually active and will be queried on whether they have been abstinent when they present to the clinic for the Final Visit or, Female sterilization; or, Sterilization of male partner; or, Implants of levonorgestrel; or, Injectable progestogen; or, Oral contraceptive (combined or progestogen only); or, Any intrauterine device (IUD) with published data showing highest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or, Spermicide plus a mechanical barrier (e. g., spermicide plus a male condom or a female diaphragm). Any other barrier methods (only if used in combination with any of the above acceptable methods) or, Any other methods with published data showing highest expected failure rate for that method is less than 1% per year.

- Formally diagnosed ICHD 5. 2.2 chronic post traumatic headache

- Have had traumatic brain injury (TBI) not more than 5 years prior to enrollment

- Medically stable as determined by Investigator

- On stabilized dosage of any headache preventive medications for 3 months prior to

screening

- On stabilized dosage of concomitant medications at discretion of investigator

- Chronic headache history only after the TBI

- Able to understand and communicate intelligibly with study observer

- Able to take oral medication, adhere to the medication regimens and perform study

procedures

- Able to read and comprehend written instructions and be willing to complete all

procedures and assessments required by protocol

- Subject is able to demonstrate willingness to participate by signing and understanding

an informed consent after full explanation of study

- Self-reported cognitive inefficiency or "brain-fog" during headache

Exclusion Criteria:

- History of hypersensitivity to triptan-like medication

- Pathology of salivary glands such as sialadenitis (e. g., Sjorgen's Syndrome, viral or

bacterial sialadenitis, or obstructive sialadenitis)

- Any condition or symptom that would knowingly alter content of saliva

- History of, symptoms or signs of ischemic cardiac, cerebrovascular or peripheral

vascular syndromes or other significant underlying cardiovascular disease. Ischemic cardiac syndromes include, but are not limited to, angina pectoris of any type (e. g. stable angina of effort and vasospastic forms of angina such as Prinzmetal variant, all forms of myocardial infarction, and silent myocardial ischemia. Cerebrovascular syndromes include, but are not limited to, strokes of any type as well as transient ischemic attacks. Peripheral vascular disease includes, but is not limited to, ischemic bowel disease.

- Any medication overuse that in the opinion of the investigator has exacerbated or

contributed to current headache pattern of subject

- Uncontrolled hypertension, severe renal impairment, severe hepatic impairment,

hemiplegic or basilar headache

- History of hypersensitivity to naratriptan or any components

- Pregnant, trying to get pregnant, or lactating

- Recent history of abuse of alcohol or other drugs that would interfere with

participation

- Participation in another investigative drug study within previous 30 days

- Chronic pain syndromes, fibromyalgia, Gulf War Syndrome, and other multisystem

diseases characterized by poor or no response to pain-reducing interventions

- Secondary gain is currently active complication to recovery (e. g., has a pending

lawsuit for injuries from MVA in which concussion was sustained)

Clinvest, Springfield, Missouri 65807, United States; Recruiting
Rhonda Cadle, RN, Phone: 417-841-3644, Email: rcadle@clinvest.com
Debbie Milligan, RN, Phone: 417-841-3625, Email: dmilligan@clinvest.com
Roger K Cady, MD, Principal Investigator
Dennis L Reeves, PhD, Sub-Investigator
Kathleen U Farmer, PsyD, Sub-Investigator
John K Dexter, MD, Sub-Investigator
Curtis P Schreiber, MD, Sub-Investigator

Carolinas Rehabilitation, Carolinas HealthCare System, Charlotte, North Carolina 28203, United States; Recruiting
Marybeth Whitney, BSN, Phone: 704-355-1409, Email: Marybeth.Whitney@carolinashealthcare.org
Flora Hammond, MD, Principal Investigator
Lori M Grafton, MD, Sub-Investigator
Andrew Dennison, MD, Sub-Investigator
Shilpa Kasuganti, MD, Sub-Investigator

Anodyne Headache and Pain Care, Dallas, Texas 75231, United States; Recruiting
Virginia Krusz, Phone: 214-750-6664, Email: nodynia@swbell.net
John C Krusz, MD, Principal Investigator

Related publications:

Baandrup L, Jensen R. Chronic post-traumatic headache--a clinical analysis in relation to the International Headache Classification 2nd Edition. Cephalalgia. 2005 Feb;25(2):132-8. Erratum in: Cephalalgia. 2005 Mar;25(3):240.

Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004;24 Suppl 1:9-160. No abstract available.

Starting date: October 2006
Ending date: January 2009
Last updated: October 22, 2008