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

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

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00487578

Enrollment

Registered

2007-06-18

Start date

2006-10-31

Completion date

2009-10-31

Last updated

2013-02-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Post Traumatic Headache

Keywords

Post traumatic headache, Head trauma, Head injury, Headache, Naratriptan

Brief summary

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.

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. 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.

Interventions

DRUGnaratriptan HCl

naratriptan 2.5mg tablet bid x 30 days OR matching placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Headache Days	Day 30	Number of headache days as measured by the Headache Diary
Headache Impact Test-6 (HIT-6) Score	Day 0, Day 30	Impact of headache symptoms on subject's life as measured by HIT-6 questionnaire scores. Possible scores range from 36 to 78. Score of 48 or less indicates headache has little impact on life. Score of 60-78 indicative of very severe impact.
Mental Efficiency Workload Test (MEWT) Performance Index Score	Day 0, Day 10, Day 30	Cognitive function as measured by Performance Index scores on the Mental Efficiency Workload Test (MEWT). On the performance index scale of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. Tests include: Simple reaction time, Running memory, Matching to sample, Math processing and a sleep scale.

Secondary

Measure	Time frame	Description
Overall Satisfaction With Medication Score	Day 30, Day 90	Subject overall satisfaction with effectiveness of the therapy as measured by score on the Satisfaction with Medication questionnaire. Scale range: Very satisfied, Satisfied, Neutral, Dissatisfied, Very dissatisfied.
Quality of Life Scores	Day 0, Day 30, Day 90	Quality of life as measured by Migraine Specific Quality of Life questionnaire (MSQ) scores. 14 questions ask how often headaches have interfered with specific daily activities in previous 4 weeks. 6-point scale ranges from None of the time to All of the time.
Sustained Treatment Effect	Day 0, Day 10, Day 30	Sustained treatment effect as measured by the MEWT Performance Index score compared to change in number of Headache Days. Results would be presented in the form of a correlation analysis. There is an expected negative correlation as performance index increases and number of headache days decrease (a correlation of -1).

Countries

United States

Participant flow

Recruitment details

Subject enrollment started in 2006 at Site 1 (headache specialty clinic). Subjects were never enrolled at 2nd site (hospital rehabilitation center). Sites 3 (pain clinic) and 4 (hospital rehabilitation center) were added in 2008. Enrollment continued until study termination October 2009.

Pre-assignment details

19 participants were screened. 7 were Screen Failures.

Participants by arm

Arm	Count
Active Naratriptan Naratriptan 2.5 mg tablet twice daily (bid) x 30 days	3
Placebo Matching Naratriptan placebo matching naratriptan 2.5 mg tablet twice daily (bid) x 30 days	9
Total	12

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	2
Overall Study	Lack of Efficacy	0	1
Overall Study	Lost to Follow-up	0	1

Baseline characteristics

Characteristic	Placebo Matching Naratriptan	Active Naratriptan	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	9 Participants	3 Participants	12 Participants
Age Continuous	37.22 years STANDARD_DEVIATION 9.65	39.66 years STANDARD_DEVIATION 10.96	37.83 years STANDARD_DEVIATION 9.53
Region of Enrollment United States	9 participants	3 participants	12 participants
Sex: Female, Male Female	7 Participants	1 Participants	8 Participants
Sex: Female, Male Male	2 Participants	2 Participants	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	3 / 3	6 / 9
serious Total, serious adverse events	0 / 3	0 / 9

Outcome results

Primary