CGRP, Estrogen, Cortisol, VIP, α-Amylase, PGE2, PGI2 and ß-Endorphin Levels in Menstrual Migraine Before and After Treximet

NCT01329562 | Completed Phase 4 Results

• 1 other identifier: 114680
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief 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 (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™.

Conditions

Menstrual Migraine

Keywords

Menstrual migraine; Menstrually-related migraine; Treximet; CGRP; calcitonin gene-related peptide

Outcome Measures

Primary Outcomes (9)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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

  From the onset of 1 menstrual migraine until 24 hours post treatment.

• Time to Pain-Free in Responders vs Non-Responders

  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

  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

  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

  From Baseline until 2 hours post treatment of 1 menstrual migraine headache.

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Treximet DRUG

Tablet for oral administration contains sumatriptan 85mg / naproxen sodium 500mg.

Also known as: Sumatriptan/Naproxen Sodium

Treximet

Placebo DRUG

A placebo tablet matching Treximet for oral administration.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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,
• 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

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Cady, Roger, M.D.: lead
• GlaxoSmithKline: collaborator

Study Sites (2)

Clinvest

Springfield, Missouri, 65807, United States

Location

University Internal Medicine Associates, Inc.

Cincinnati, Ohio, 45267-0535, United States

Location

Related Publications (6)

• 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.

  PMID: 16618254 BACKGROUND

• Martin 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.

  PMID: 16412160 BACKGROUND

• Cady R, Dodick DW. Diagnosis and treatment of migraine. Mayo Clin Proc. 2002 Mar;77(3):255-61. doi: 10.4065/77.3.255.

  PMID: 11888029 BACKGROUND

• Durham 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.

  PMID: 16927957 BACKGROUND

• Nappi 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.

  PMID: 16123089 BACKGROUND

• Bellamy 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.

  PMID: 16412148 BACKGROUND

MeSH Terms

Interventions

sumatriptan-naproxen; Sumatriptan; Naproxen

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Roger Cady
• Organization: Clinvest/A Division of Banyan Group Inc.

jtarrasch@clinvest.com

417-890-7888

Study Officials

• Roger K Cady, MD

  Clinvest

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2011
• First Posted: April 6, 2011
• Study Start: May 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: April 9, 2014
• Results First Posted: April 9, 2014

Record last verified: 2014-03

Locations

US (2)