Menstrual MigrainePhase 4NCT01329562
CGRP, Estrogen, Cortisol, VIP, α-Amylase, PGE2, PGI2 and ß-Endorphin Levels in Menstrual Migraine Before and After Treximet
A Phase 4 study testing Treximet in people with Menstrual Migraine, run by Cady, Roger, M.D. at 2 sites in United States.
Trial summary
The purpose of this study is to (1) evaluate pain-free efficacy of Treximet™ following treatment of menstrual migraine, (2) investigate levels of Calcitonin gene-related peptide (CGRP), estrogen, cortisol, vasoactive intestinal peptide (VIP), alpha (a)-amylase, Prostaglandin E2 (PGE2), Prostaglandin I2 (PGI2) and beta… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Menstrual Migraine
- What is being tested?
- Treximet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2011to Jun 2012
- 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 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Subject
- is female between the ages of 18-45 and, if of 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,
- History of bilateral tubal ligation
- Sterilization of male partner; or,
- Implants of levonorgestrel; or,
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- Injectable progestogen; or,
- Oral contraceptive (combination therapy with ethinyl estradiol plus a progestin) with a placebo week every 1-3 months; or,
- Any intrauterine device (IUD) with published data showing that the 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); or,
- Any other barrier methods (only if used in combination with any of the above acceptable methods); or,
- Any other methods with published data showing that the highest expected failure rate for that method is less than 1% per year.
- is formally diagnosed with International Classification of Headache Disorders (ICHD) menstrual migraine
- has regular and predictable monthly menstrual cycles within a range of 22-32 days for the past 3 cycles.
- has fewer than 15 headache days per month in past 3 months
- has headache that, if left untreated, would have at least 1 symptom of migraine (nausea, vomiting, photophobia, or phonophobia) or respond to a triptan or ergotamine-containing medication with at least 50% of headaches
- has a history of reliably predicting menstrual migraine headache onset at least 70% of the time
- is medically stable as determined by the Investigator
- if taking any concomitant medications, is on a stabilized dosage at the discretion of the investigator
- is able to understand and communicate intelligibly with the study observer
- is able to take oral medication, adhere to the medication regimens and perform study procedures
- is able to read and comprehend written instructions and be willing to complete all procedures and assessments required by this protocol
- is able to demonstrate the willingness to participate by signing and understanding an informed consent after full explanation of the study
Who cannot join
- Subject
- has a history of serotonin syndrome.
- has any medical condition that, in the opinion of the investigator, could alter the response to study medication or confound the results of the study (ie. pathology of the salivary glands such as viral or bacterial sialadenitis or obstructive sialadenitis or Sjögren's Syndrome)
- is of childbearing potential and not using adequate contraceptive measures
- has history of retinal, basilar or hemiplegic migraine, cluster headache, or secondary headaches (such as due to trauma, infection, alterations of homeostasis, ear, nose and throat (ENT) or psychiatric disorders, cranial or cervical disorders or neuralgias)
- in the investigator's opinion, is likely to have unrecognized cardiovascular or cerebrovascular disease (based on history or the presence of risk factors including but not limited to, hypertension, hypercholesterolemia, smoker, obesity, diabetes, or family history of coronary artery disease)
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- has blood pressure equal to or greater than 160/90 millimeters of mercury (mmHg) in 2 out of 3 blood pressure (BP) measurements at screening or is taking any angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker
- has a history of significant congenital heart disease, cardiac arrhythmias requiring medication, or a history of a clinically significant electrocardiogram abnormality that, in the investigator's opinion, contraindicates participation in this study
- has evidence or history of any ischemic vascular diseases including: ischemic heart disease, ischemic abdominal syndromes, peripheral vascular disease or Raynaud's Syndrome, or signs/symptoms consistent with any of the above
- has evidence or history of central nervous system pathology including stroke and/or transient ischemic attacks (TIAs), epilepsy or structural brain lesions which lower the convulsive threshold; or has been treated with an antiepileptic drug for seizure control within 5 years prior to screening
- has a history of impaired hepatic or renal function that, in the investigator's opinion, contraindicates participation in this study
- has hypersensitivity, intolerance, or contraindication to the use of any triptan, non-steroidal anti-inflammatory drug (NSAID) or aspirin (including all sumatriptan and naproxen preparations) or has nasal polyps and asthma
- is currently taking, or has taken in the previous three months, a migraine prophylactic medication containing methysergide; or is taking a migraine or menstrual migraine prophylactic medication that is not stabilized (eg. Perimenstrual use of triptans and estradiol patches)
- has a recent history of regular use of opioids or barbiturates for treatment of their migraine headache and/or other non-migraine pain or any medication overuse that in the opinion of the investigator has exacerbated or contributed to the current headache pattern of the subject. Overuse is defined as an average of 10 days per month over the last 6 months.
- has taken, or plans to take, a monoamine oxidase inhibitor (MAOI), including herbal preparations containing St. John's Wort (Hypericum perforatum), anytime within the 2 weeks prior to screening through 2 weeks post final study treatment.
- is currently taking and plans to continue an oral steroid any time from screening through onset of menses that will be treated with study medication (at the discretion of the investigator)
- has history of any bleeding disorder or is currently taking any anti-coagulant or any antiplatelet agent.
- has evidence or history of any gastrointestinal surgery or gastrointestinal (GI) ulceration or perforation in the past six months, gastrointestinal bleeding in the past year; or evidence or history of inflammatory bowel disease
- is pregnant, actively trying to become pregnant, or breast feeding
- has evidence of alcohol or substance abuse within the last year or any concurrent medical or psychiatric condition which, in the investigator's judgment, will likely interfere with the study conduct, subject cooperation, or evaluation and interpretation of the study results, or which otherwise contraindicates participation in this clinical trial.
- has participated in an investigational drug trial within the previous four weeks or plans to participate in another study at any time during this study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University Internal Medicine Associates, Inc.
Cincinnati, Ohio, 45267-0535
Clinvest
Springfield, Missouri, 65807
About this study
Official title: Evaluation of CGRP, Estrogen, Cortisol, VIP, α-Amylase, PGE2, PGI2 and ß-Endorphin Levels in Saliva of Menstrual Migraine Patients Before and After Treatment With Treximet™
The purpose of this study is to (1) evaluate pain-free efficacy of Treximet™ following treatment of menstrual migraine, (2) investigate levels of Calcitonin gene-related peptide (CGRP), estrogen, cortisol, vasoactive intestinal peptide (VIP), alpha (a)-amylase, Prostaglandin E2 (PGE2), Prostaglandin I2 (PGI2) and beta (ß)-endorphin in saliva before and after Treximet™, (3) evaluate efficacy of Treximet™ to return to baseline levels following treatment, and (4) correlate estrogen in saliva vs. urinary estradiol at mid-luteal, onset of menstrually-related migraine, and after successful treatment with Treximet™.
Read the detailed description
This double-blind multi-site study will be conducted to enroll 40 evaluable participants. All subjects will be medically stable at enrollment and be on a stabilized dosage of daily medications.
At Visit 1 (Baseline) following Informed Consent, a physical and neurological exam, baseline electrocardiogram (ECG), and vital signs will be completed. A urine pregnancy test will be collected by all subjects of childbearing potential. Routine labs (electrolyte panel with creatinine, alanine aminotransferase (ALT) / aspartate aminotransferase (AST), a luteinizing hormone (LH) lab (for menstrual cycle staging) and a baseline saliva sample (for CGRP, estrogen, cortisol, VIP, a-amylase, PGI2, PGE2 and β-endorphin analysis) will be collected. Subjects should be headache-free at Visit 1. A medical, headache, and medication history will be collected on all subjects and eligible subjects will be randomized 1:1 to Group A or Group B. Group A will receive Treximet™ (sumatriptan succinate 85 milligrams (mg) and naproxen sodium 500 mg) 1 tablet. Group B will be provided 1 matching placebo tablet. Subjects will be instructed to not start study medication until notified by study staff that lab results were normal and they are eligible to proceed. Subjects will be instructed to treat as early as possible following the onset of a typical menstrual headache. Groups A and B will be provided with Treximet™ 1 tablet for rescue between 2 and 24 hours for persistent or recurring headache. Subjects will receive a Diary and instructions on Digital Versatile Disc (DVD) regarding documentation. Migraine associated symptoms (ie nausea, vomiting, light sensitivity, or sound sensitivity) will be collected as well as sleeplessness, difficulty thinking other bodily pain, and menstrual associated symptoms (to include intensity of menstrual cramps).
Subjects will be given kits with written instructions for collection of urine and saliva samples and additional saliva instructions on DVD. All subjects will be given LH testing kits to define the time of ovulation. Diary documentation begins at the time of ovulation. They will collect baseline saliva and first morning urine samples during the mid-luteal time period for two consecutive days, which is defined as 4-7 days after the LH surge. Subjects will also be instructed to begin collection of saliva 48 hours prior to the start of menses at 8:00 am, 2:00 pm, and 8:00 pm for two days or until menstrual migraine occurs. They also will collect a first morning urine sample on the two mornings prior to menses. At the point of headache onset, subjects will be instructed to collect saliva at onset of pain, time of treatment, 2 and 24 hours following treatment, at pain free, 2 hours after pain free, and 24 hours after pain free. Subjects will also be instructed to collect a urine specimen when they are pain free following treatment with study medication. Subjects will document migraine associated symptoms, menstrual associated symptoms, and recurrence symptoms at all saliva collection time points in the provided Diary per instruction.
Subjects should be instructed to phone the study coordinator at the end of the menstrual cycle to return for Visit 2 within 7 days.
_________________________
At Visit 2 (Review) Diaries will be reviewed and frozen saliva and urine samples will be returned to the clinic. Subjects must meet the following criteria for urine and saliva analysis:
- Diary review indicates that headache would have, if left untreated, at least one symptom of migraine (nausea, vomiting, phonophobia, or photophobia) . And
- Headache was associated with the onset of menses
And
- Saliva and urine samples are returned to the clinic.
Medical and medication history will be updated and adverse events collected. A urine pregnancy test will be collected by all subjects of childbearing potential. Drug accountability and compliance will be assessed.
- Conditions
- Menstrual Migraine
- Being tested
- Treximet, Placebo
- Keywords
- Menstrual migraine, Menstrually-related migraine, Treximet, CGRP, calcitonin gene-related peptide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TreximetDrug
Also called Sumatriptan/Naproxen Sodium
Tablet for oral administration contains sumatriptan 85mg / naproxen sodium 500mg.
PlaceboDrug
A placebo tablet matching Treximet for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| Treximet | Active comparator | Subjects randomized to Group A will be provided with 1 tablet of Treximet to be taken at onset of menstrual migraine headache pain.
All subjects will be provided with 1 tablet of Treximet for treatment of persistent or recurring headache between 2 and 24 hours following treatment with study medication at headache onset. Receives: Drug: Treximet |
| Placebo | Placebo comparator | Subjects randomized to Group B will be provided with 1 tablet of placebo to be taken at onset of menstrual migraine headache pain.
All subjects will be provided with 1 tablet of Treximet for treatment of persistent or recurring headache between 2 and 24 hours following treatment with study medication at headache onset. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Migraine Recurrence
Number of subjects either pain free or mild at 2 hours then pain level increases within 24 hours following treatment with Treximet versus (vs.) Placebo for 1 menstrual migraine.
0-3 pain scale with 0=No Pain, 1=Mild, 2=Moderate,and 3=Severe.
Measured: From onset of a single menstrual migraine episode to 24 hours post menstrual migraine treatment.
Time to Pain Free
Duration of 1 menstrual migraine from time of treatment at menstrual migraine headache onset until pain free in Treximet vs. Placebo arms.
0-3 pain scale with 0=No Pain, 1=Mild, 2=Moderate, and 3=Severe.
Measured: From onset of 1 menstrual migraine headache until pain free.
Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment
Vasoactive Intestinal Peptide (VIP), Prostaglandin E2 (PGE2), Cortisol, Prostaglandin I2 (PGI2), Estradiol, and β-endorphin** levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Treximet vs. Placebo arms for 1 menstrual migraine headache * This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure. Calcitonin Gene-Related Peptide (CGRP) and α-amylase both have their own outcome measure reported individually.
**β-endorphin levels were not assayed due to limitations on saliva sample volumes.
Measured: From Baseline until 2 hours post treatment of 1 menstrual migraine headache
CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment
CGRP levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Treximet vs. Placebo arms for 1 menstrual migraine headache
- This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
Measured: From Baseline until 2 hours post treatment for 1 menstrual migraine headache
α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment
α-Amylase levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Treximet vs. Placebo arm for 1 menstrual migraine headache
- This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
Measured: From Baseline until 2 hours post treatment for 1 menstrual migraine headache
Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free.
VIP, PGE2, Cortisol, PGI2, Estradiol, and β-endorphin** levels collected at Menstrual Migraine Headache Onset, Migraine Headache Free and 24 Hours Migraine Headache Free in Treximet vs. Placebo arm for 1 menstrual migraine headache.
- This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure. CGRP and α-amylase both have their own outcome measure reported individually.
**β-endorphin levels were not assayed due to limitations on saliva sample volumes.
Measured: From baseline to 24 hours post headache gone for 1 menstrual migraine headache.
CGRP Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free.
CGRP levels collected at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Treximet vs. Placebo arm for 1 menstrual migraine headache.
- This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
Measured: From baseline to 24 hours post headache gone for 1 menstrual migraine headache
α-Amylase Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free.
α-Amylase levels collected at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Treximet vs. Placebo arm for 1 menstrual migraine headache
- This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
Measured: From baseline to 24 hours post headache gone for 1 menstrual migraine headache
Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free.
Correlation of mean estrogen levels in saliva and urine estradiol at mid luteal, menstrual migraine headache onset*, and at migraine headache free following treatment with Treximet vs. Placebo for 1 menstrual migraine headache
*Urine estradiol levels were not collected at migraine onset, therefore; correlations could not be completed for that time point.
Measured: From mid luteal phase and for the duration of 1 menstrual migraine headache and until headache free
Secondary outcomes (9)
Migraine Recurrence Responders vs Non-Responders
Number of subjects either pain-free or mild at 2 hours then pain level increases within 24 hours following treatment in Treximet vs. Placebo arm for 1 menstrual migraine headache with Treximet vs. Placebo in responders* vs. non-responders.
0-3 Pain Scale with 0=No Pain, 1=Mild, 2=Moderate, and 3=Severe
*A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment.
A non-responder is one that fails to meet the responder criteria.
Measured: From the onset of 1 menstrual migraine until 24 hours post treatment.
Time to Pain-Free in Responders vs Non-Responders
Duration of time from treatment at menstrual migraine headache onset until pain-free in Treximet vs. Placebo arms in responders* vs. non-responders for 1 menstrual migraine.
0-3 Pain Scale, with 0=No Pain, 1=Mild, 2=Moderate, and 3=Severe.
*A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment.
A non-responder is one that fails to meet the responder criteria.
Measured: From the onset of 1 menstrual migraine headache until pain-free.
Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders
VIP, PGE2, Cortisol, PGI2, Estradiol, and β-endorphin levels collected for 1 menstrual migraine headache at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Treximet vs. Placebo arms in responders vs. non-responders*.
*This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same unit of measure. CGRP and α-amylase both have their own outcome measure reported individually.
**β-endorphin levels were not assayed due to limitations on saliva sample volumes.
***A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment.
A non-responder is one that fails to meet the responder criteria.
Measured: From Baseline until 2 Hours post menstrual migraine treatment for 1 menstrual migraine headache.
CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders
CGRP levels collected for 1 menstrual migraine headache at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders**.
*This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
**A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment.
A non-responder is one that fails to meet the responder criteria.
Measured: From Baseline until 2 Hours post menstrual migraine treatment for 1 menstrual migraine headache.
α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders
α-Amylase levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders*.
*A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment.
A non-responder is one that fails to meet the responder criteria.
Measured: From Baseline until 2 hours post treatment of 1 menstrual migraine headache.
Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders
VIP, PGE2, Cortisol, PGI2, Estradiol, and β-endorphin levels collected for 1 menstrual migraine headache at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders*.
*This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure. CGRP and α-amylase both have their own outcome measure reported individually.
**β-endorphin levels were not assayed due to limitations on saliva sample volumes.
***A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment. A non-responder is one that fails to meet the responder criteria.
Measured: From Baseline for the duration of 1 menstrual migraine headache, an estimated 7 days
CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders
CGRP levels collected for 1 menstrual migraine headache at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders**.
*This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
**A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment.
A non-responder is one that fails to meet the responder criteria.
Measured: From Baseline to 24 hours post headache gone for 1 menstrual migraine.
α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders
α-Amylase levels collected for 1 menstrual migraine at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders**.
*This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
**A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment.
A non-responder is one that fails to meet the responder criteria.
Measured: From Baseline from 24 hours post migraine gone for 1 menstrual migraine.
Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders
Correlation of mean estrogen levels in saliva and urine estradiol at mid-luteal, menstrual migraine headache onset* and at migraine headache free following treatment in responders vs. non-responders**.
*Urine estradiol levels were not collected at migraine onset, therefore; correlations could not be completed for that time point.
***A responder is defined as those who at the time of two hours post treatment reported mild or no pain. Additionally, these subjects could not have taken a rescue medication or have a pain level increase within 24 hours post treatment.
A non-responder is one that fails to meet the responder criteria.
Measured: From mid luteal phase and for the duration of 1 menstrual migraine until headache free.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2011 (estimated)
- Study startMay 2011
- Primary completionJun 2012
- Study completionJun 2012
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 (6)Papers the sponsor has linked to this study.
- Other trials for Menstrual MigraineStudies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cady, Roger, M.D.
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Roger K Cady, MD, Principal investigator, Clinvest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01329562
- Sponsor's protocol ID
- 114680
- Status last verified
- Mar 2014
- First submitted
- 17 Mar 2011
- Last updated
- 9 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Martin VT, Behbehani M. Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis--part 2. Headache. 2006 Mar;46(3):365-86. doi: 10.1111/j.1526-4610.2006.00370.x.
PubMed 16618254Martin VT, Wernke S, Mandell K, Ramadan N, Kao L, Bean J, Liu J, Zoma W, Rebar R. Symptoms of premenstrual syndrome and their association with migraine headache. Headache. 2006 Jan;46(1):125-37. doi: 10.1111/j.1526-4610.2006.00306.x.
PubMed 16412160Cady R, Dodick DW. Diagnosis and treatment of migraine. Mayo Clin Proc. 2002 Mar;77(3):255-61. doi: 10.4065/77.3.255.
PubMed 11888029Durham PL. Calcitonin gene-related peptide (CGRP) and migraine. Headache. 2006 Jun;46 Suppl 1(Suppl 1):S3-8. doi: 10.1111/j.1526-4610.2006.00483.x.
PubMed 16927957Nappi RE, Sances G, Brundu B, De Taddei S, Sommacal A, Ghiotto N, Polatti F, Nappi G. Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval. Hum Reprod. 2005 Dec;20(12):3423-8. doi: 10.1093/humrep/dei260. Epub 2005 Aug 25.
PubMed 16123089Bellamy JL, Cady RK, Durham PL. Salivary levels of CGRP and VIP in rhinosinusitis and migraine patients. Headache. 2006 Jan;46(1):24-33. doi: 10.1111/j.1526-4610.2006.00294.x.
PubMed 16412148
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of CGRP, Estrogen, Cortisol, VIP, α-Amylase, PGE2, PGI2 and ß-Endorphin Levels in Saliva of Menstrual Migraine Patients Before and After Treatment With Treximet™
- ClinicalTrials.gov ID
- NCT01329562
- Acronym / sponsor ID
- 114680
- Conditions
- Menstrual Migraine
- Keywords
- Menstrual migraine, Menstrually-related migraine, Treximet, CGRP, calcitonin gene-related peptide
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Cady, Roger, M.D.
- Collaborators
- GlaxoSmithKline
- Study start
- May 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 6 Apr 2011 (estimated)
- Results
- Posted 9 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to (1) evaluate pain-free efficacy of Treximet™ following treatment of menstrual migraine, (2) investigate levels of Calcitonin gene-related peptide (CGRP), estrogen, cortisol, vasoactive intestinal peptide (VIP), alpha (a)-amylase, Prostaglandin E2 (PGE2), Prostaglandin I2 (PGI2) and beta (ß)-endorphin in saliva before and after Treximet™, (3) evaluate efficacy of Treximet™ to return to baseline levels following treatment, and (4) correlate estrogen in saliva vs. urinary estradiol at mid-luteal, onset of menstrually-related migraine, and after successful treatment with Treximet™.
Detailed description
This double-blind multi-site study will be conducted to enroll 40 evaluable participants. All subjects will be medically stable at enrollment and be on a stabilized dosage of daily medications.
At Visit 1 (Baseline) following Informed Consent, a physical and neurological exam, baseline electrocardiogram (ECG), and vital signs will be completed. A urine pregnancy test will be collected by all subjects of childbearing potential. Routine labs (electrolyte panel with creatinine, alanine aminotransferase (ALT) / aspartate aminotransferase (AST), a luteinizing hormone (LH) lab (for menstrual cycle staging) and a baseline saliva sample (for CGRP, estrogen, cortisol, VIP, a-amylase, PGI2, PGE2 and β-endorphin analysis) will be collected. Subjects should be headache-free at Visit 1. A medical, headache, and medication history will be collected on all subjects and eligible subjects will be randomized 1:1 to Group A or Group B. Group A will receive Treximet™ (sumatriptan succinate 85 milligrams (mg) and naproxen sodium 500 mg) 1 tablet. Group B will be provided 1 matching placebo tablet. Subjects will be instructed to not start study medication until notified by study staff that lab results were normal and they are eligible to proceed. Subjects will be instructed to treat as early as possible following the onset of a typical menstrual headache. Groups A and B will be provided with Treximet™ 1 tablet for rescue between 2 and 24 hours for persistent or recurring headache. Subjects will receive a Diary and instructions on Digital Versatile Disc (DVD) regarding documentation. Migraine associated symptoms (ie nausea, vomiting, light sensitivity, or sound sensitivity) will be collected as well as sleeplessness, difficulty thinking other bodily pain, and menstrual associated symptoms (to include intensity of menstrual cramps).
Subjects will be given kits with written instructions for collection of urine and saliva samples and additional saliva instructions on DVD. All subjects will be given LH testing kits to define the time of ovulation. Diary documentation begins at the time of ovulation. They will collect baseline saliva and first morning urine samples during the mid-luteal time period for two consecutive days, which is defined as 4-7 days after the LH surge. Subjects will also be instructed to begin collection of saliva 48 hours prior to the start of menses at 8:00 am, 2:00 pm, and 8:00 pm for two days or until menstrual migraine occurs. They also will collect a first morning urine sample on the two mornings prior to menses. At the point of headache onset, subjects will be instructed to collect saliva at onset of pain, time of treatment, 2 and 24 hours following treatment, at pain free, 2 hours after pain free, and 24 hours after pain free. Subjects will also be instructed to collect a urine specimen when they are pain free following treatment with study medication. Subjects will document migraine associated symptoms, menstrual associated symptoms, and recurrence symptoms at all saliva collection time points in the provided Diary per instruction.
Subjects should be instructed to phone the study coordinator at the end of the menstrual cycle to return for Visit 2 within 7 days.
_________________________
At Visit 2 (Review) Diaries will be reviewed and frozen saliva and urine samples will be returned to the clinic. Subjects must meet the following criteria for urine and saliva analysis:
- Diary review indicates that headache would have, if left untreated, at least one symptom of migraine (nausea, vomiting, phonophobia, or photophobia) . And
- Headache was associated with the onset of menses
And
- Saliva and urine samples are returned to the clinic.
Medical and medication history will be updated and adverse events collected. A urine pregnancy test will be collected by all subjects of childbearing potential. Drug accountability and compliance will be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treximet | Active comparator | Drug: TreximetSubjects randomized to Group A will be provided with 1 tablet of Treximet to be taken at onset of menstrual migraine headache pain. All subjects will be provided with 1 tablet of Treximet for treatment of persistent or recurring headache between 2 and 24 hours following treatment with study medication at headache onset. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects randomized to Group B will be provided with 1 tablet of placebo to be taken at onset of menstrual migraine headache pain. All subjects will be provided with 1 tablet of Treximet for treatment of persistent or recurring headache between 2 and 24 hours following treatment with study medication at headache onset. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (23 listed)
- Subject
- is female between the ages of 18-45 and, if of child-bearing potential, has a negative pregnancy test (urine or serum) at screen, and agrees to one of the following:
- is formally diagnosed with International Classification of Headache Disorders (ICHD) menstrual migraine
- has regular and predictable monthly menstrual cycles within a range of 22-32 days for the past 3 cycles.
- has fewer than 15 headache days per month in past 3 months
Key exclusion criteria (21 listed)
- Subject
- has a history of serotonin syndrome.
- has any medical condition that, in the opinion of the investigator, could alter the response to study medication or confound the results of the study (ie. pathology of the salivary glands such as viral or bacterial sialadenitis or obstructive sialadenitis or Sjögren's Syndrome)
- is of childbearing potential and not using adequate contraceptive measures
- has history of retinal, basilar or hemiplegic migraine, cluster headache, or secondary headaches (such as due to trauma, infection, alterations of homeostasis, ear, nose and throat (ENT) or psychiatric disorders, cranial or cervical disorders or neuralgias)
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 |
|---|---|---|
| TreximetAlso: Sumatriptan/Naproxen SodiumTablet for oral administration contains sumatriptan 85mg / naproxen sodium 500mg. | Drug | Treximet |
| PlaceboA placebo tablet matching Treximet for oral administration. | Drug | Placebo |
Primary outcome
Migraine Recurrence
Time frame: From onset of a single menstrual migraine episode to 24 hours post menstrual migraine treatment.
Number of subjects either pain free or mild at 2 hours then pain level increases within 24 hours following treatment with Treximet versus (vs.) Placebo for 1 menstrual migraine. 0-3 pain scale with 0=No Pain, 1=Mild, 2=Moderate,and 3=Severe.
Time to Pain Free
Time frame: From onset of 1 menstrual migraine headache until pain free.
Duration of 1 menstrual migraine from time of treatment at menstrual migraine headache onset until pain free in Treximet vs. Placebo arms. 0-3 pain scale with 0=No Pain, 1=Mild, 2=Moderate, and 3=Severe.
Biomarkers Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment
Time frame: From Baseline until 2 hours post treatment of 1 menstrual migraine headache
Vasoactive Intestinal Peptide (VIP), Prostaglandin E2 (PGE2), Cortisol, Prostaglandin I2 (PGI2), Estradiol, and β-endorphin** levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Treximet vs. Placebo arms for 1 menstrual migraine headache * This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure. Calcitonin Gene-Related Peptide (CGRP) and α-amylase both have their own outcome measure reported individually. **β-endorphin levels were not assayed due to limitations on saliva sample volumes.
CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment
Time frame: From Baseline until 2 hours post treatment for 1 menstrual migraine headache
CGRP levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Treximet vs. Placebo arms for 1 menstrual migraine headache * This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment
Time frame: From Baseline until 2 hours post treatment for 1 menstrual migraine headache
α-Amylase levels collected at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Treximet vs. Placebo arm for 1 menstrual migraine headache * This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free.
Time frame: From baseline to 24 hours post headache gone for 1 menstrual migraine headache.
VIP, PGE2, Cortisol, PGI2, Estradiol, and β-endorphin** levels collected at Menstrual Migraine Headache Onset, Migraine Headache Free and 24 Hours Migraine Headache Free in Treximet vs. Placebo arm for 1 menstrual migraine headache. * This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure. CGRP and α-amylase both have their own outcome measure reported individually. **β-endorphin levels were not assayed due to limitations on saliva sample volumes.
CGRP Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free.
Time frame: From baseline to 24 hours post headache gone for 1 menstrual migraine headache
CGRP levels collected at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Treximet vs. Placebo arm for 1 menstrual migraine headache. * This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
α-Amylase Measured at Menstrual Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free.
Time frame: From baseline to 24 hours post headache gone for 1 menstrual migraine headache
α-Amylase levels collected at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Treximet vs. Placebo arm for 1 menstrual migraine headache * This endpoint was separated into 3 outcome measures as all biomarkers were not reported in the same units of measure.
Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid Luteal and at Menstrual Migraine Headache Free.
Time frame: From mid luteal phase and for the duration of 1 menstrual migraine headache and until headache free
Correlation of mean estrogen levels in saliva and urine estradiol at mid luteal, menstrual migraine headache onset*, and at migraine headache free following treatment with Treximet vs. Placebo for 1 menstrual migraine headache *Urine estradiol levels were not collected at migraine onset, therefore; correlations could not be completed for that time point.
9 secondary outcomes
Migraine Recurrence Responders vs Non-Responders
Time frame: From the onset of 1 menstrual migraine until 24 hours post treatment.
Time to Pain-Free in Responders vs Non-Responders
Time frame: From the onset of 1 menstrual migraine headache until pain-free.
Biomarkers Measured at Baseline, Menstrual Migraine Onset, and 2 Hours Post Treatment in Responders vs Non-Responders
Time frame: From Baseline until 2 Hours post menstrual migraine treatment for 1 menstrual migraine headache.
CGRP Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post-Treatment in Responders vs Non-Responders
Time frame: From Baseline until 2 Hours post menstrual migraine treatment for 1 menstrual migraine headache.
α-Amylase Measured at Baseline, Menstrual Migraine Headache Onset, and 2 Hours Post Treatment in Responders vs Non-Responders
Time frame: From Baseline until 2 hours post treatment of 1 menstrual migraine headache.
Biomarkers Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders
Time frame: From Baseline for the duration of 1 menstrual migraine headache, an estimated 7 days
CGRP Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders
Time frame: From Baseline to 24 hours post headache gone for 1 menstrual migraine.
α-Amylase Measured at Menstrual Migraine Headache Onset, Migraine Headache Free, and 24 Hours Migraine Headache Free in Responders vs Non-Responders
Time frame: From Baseline from 24 hours post migraine gone for 1 menstrual migraine.
Correlation of Mean Estrogen Levels in Saliva and Urine Estradiol at Mid-Luteal and at Menstrual Migraine Headache Free in Responders vs Non-Responders
Time frame: From mid luteal phase and for the duration of 1 menstrual migraine until headache free.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16618254Martin VT, Behbehani M. Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis--part 2. Headache. 2006 Mar;46(3):365-86. doi: 10.1111/j.1526-4610.2006.00370.x.
- Background: PubMed 16412160Martin VT, Wernke S, Mandell K, Ramadan N, Kao L, Bean J, Liu J, Zoma W, Rebar R. Symptoms of premenstrual syndrome and their association with migraine headache. Headache. 2006 Jan;46(1):125-37. doi: 10.1111/j.1526-4610.2006.00306.x.
- Background: PubMed 11888029Cady R, Dodick DW. Diagnosis and treatment of migraine. Mayo Clin Proc. 2002 Mar;77(3):255-61. doi: 10.4065/77.3.255.
- Background: PubMed 16927957Durham PL. Calcitonin gene-related peptide (CGRP) and migraine. Headache. 2006 Jun;46 Suppl 1(Suppl 1):S3-8. doi: 10.1111/j.1526-4610.2006.00483.x.
- Background: PubMed 16123089Nappi RE, Sances G, Brundu B, De Taddei S, Sommacal A, Ghiotto N, Polatti F, Nappi G. Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval. Hum Reprod. 2005 Dec;20(12):3423-8. doi: 10.1093/humrep/dei260. Epub 2005 Aug 25.
- Background: PubMed 16412148Bellamy JL, Cady RK, Durham PL. Salivary levels of CGRP and VIP in rhinosinusitis and migraine patients. Headache. 2006 Jan;46(1):24-33. doi: 10.1111/j.1526-4610.2006.00294.x.
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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.
Roger K Cady, MD principal investigator
Clinvest
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Treximet in people with Menstrual Migraine, run by Cady, Roger, M.D. at 2 sites 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 23 inclusion and 21 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: finished, as of the sponsor's last update on 9 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 9 Apr 2014). 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?
Migraine Recurrence (time frame: From onset of a single menstrual migraine episode to 24 hours post menstrual migraine treatment.). The study lists 9 primary outcomes in all. 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 NCT01329562, which also lists 6 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 9 Apr 2014.