Calcitonin Gene-related Peptide Levels in Chronic Migraine

NCT01071096 | Completed Phase 4 Results

• 1 other identifier: 10-001AL
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

Twenty patients will be enrolled in a 2-site, 7-month, double-blind study conducted to evaluate a reduction in headache days and attacks and calcitonin gene-related peptide (CGRP) levels in saliva following treatment with OnabotulinumtoxinA versus saline. Eligible patients will be randomized and receive injections of OnabotulinumtoxinA or Saline at Visit 1. Following 3 months plus a 1 month wash out, patients will receive cross-over injections at Visit 5. Patients will return for monthly visits and exit the study at Visit 8. Patients will collect saliva at monthly intervals and document in a daily headache diary throughout the study .

Conditions

Chronic Migraine

Keywords

Botox; OnabotulinumtoxinA; Chronic Migraine; Calcitonin Gene-Related Peptide; Saliva

Outcome Measures

Primary Outcomes (2)

• Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7.

  Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary.

  Baseline (collected historically at screening) versus (vs.) Month (Mo) 1, Mo 2, Mo 3, Mo 4, Mo 5, Mo 6, and Mo 7

• Change in Number of Headache Days Per Month From Baseline to Month 1 (M1), Month 1 to Month 2 (M2), and Month 2 to Month 3 (M3).

  Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary.

  Baseline (collected historically at screening) vs. Mo 1, Mo 1 vs. Mo 2, Mo 2 vs. Mo 3, Mo 3 vs. Mo 4, Mo 4 vs. Mo 5, Mo 5 vs. Mo 6, and Mo 6 vs. Mo 7

Secondary Outcomes (3)

• Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP)

  Baseline levels collected for OnabotulinumtoxinA and Saline treatment during Months 1 through 7

• Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline

  For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3

• Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders

  For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3 at Baseline level (inter-ictal) and at onset of headache that is one degree worse than Baseline level and that will be treated with acute therapy

Study Arms (2)

OnabotulinumtoxinA

ACTIVE COMPARATOR

Minimum dose of 155 international units (U) OnabotulinumtoxinA Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas.

Drug: OnabotulinumtoxinA

Saline

PLACEBO COMPARATOR

155 U Saline administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas.

Drug: Saline

Interventions

OnabotulinumtoxinA DRUG

Minimum dose of 155 U OnabotulinumtoxinA Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas. Subjects will continue to monitor headache symptoms with a headache diary and collect saliva samples as instructed. At investigator's discretion, additional 40 U OnabotulinumtoxinA Purified Neurotoxin Complex may be administered unilaterally or bilaterally, using follow-the-pain paradigm.

Also known as: Botulinum Toxin Type A Purified Neurotoxin Complex, Botox

OnabotulinumtoxinA

Saline DRUG

155 U Saline administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas. Subjects will continue to monitor headache using a headache diary and collect saliva samples as instructed. At investigator's discretion, additional Saline may be administered unilaterally or bilaterally, using follow-the-pain paradigm.

Also known as: Placebo

Saline

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• must be outpatient, male or female, of any race, between 18 and 65 years of age.
• if female of childbearing potential must have negative pregnancy test result at Screening Visit and practice reliable method of contraception.
• A female is considered of childbearing potential unless she is post menopausal for at least 12 months prior to administration of study drug, without a uterus and/or both ovaries or has been surgically sterilized for at least 6 months prior to study drug administration.
• Reliable methods of contraception are: 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; or, History of bilateral tubal ligation; or, 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 IUD's meet this criterion) in use at least 30 days prior to study drug administration; or, Spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a female diaphragm); or, Any other barrier methods (only is used in combination with any of the above acceptable methods) in use at least 14 days prior to study drug administration; or, Any other methods with published data showing that the highest expected failure rate for that methods is less than 1% per year.
• must have history of chronic migraine (with or without aura) according to the criteria proposed by the Headache Classification Committee of the International Headache Society (IHS) for at least 3 months prior to enrollment.
• must be able to understand the requirements of the study including maintaining a headache Diary, and signing informed consent.
• must be in good general health as determined by investigator.
• if taking migraine preventive, must be on a stable dose of preventive medication for at least 3 months prior to screening.

You may not qualify if:

• if female, is pregnant, planning to become pregnant during the study period, is breast feeding, or is of childbearing potential and not practicing a reliable form of birth control.
• has headache disorders outside IHS-defined chronic migraine definition.
• has evidence of underlying pathology contributing to their headaches.
• has any pathology of the salivary glands such as sialadenitis (e.g. Sjogren's syndrome, viral or bacterial sialadenitis) or condition or symptom that would alter the content of saliva.
• has any medical condition that may increase their risk with exposure to OnabotulinumtoxinA including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function.
• has profound atrophy or weakness of muscles in the target areas of injection.
• has skin conditions or infections at any of the injection sites.
• has allergy or sensitivities to any component of the test medication.
• who in the opinion of the investigator, has active major psychiatric or depressive disorders including alcohol/drug abuse.
• meets International Headache Society criteria for Medication Overuse with opioid or butalbital containing products.
• is planning or requiring surgery during the study.
• has a history of poor compliance with medical treatment.
• is currently participating in an investigational drug study or has participated in an investigational drug study within the previous 30 days of the screening visit.

Sponsors & Collaborators

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

Study Sites (2)

Clinvest

Springfield, Missouri, 65807, United States

Location

Island Neurological Associates, P.C.

Plainview, New York, 11803, United States

Location

Related Publications (7)

• 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

• Cady RK, Vause CV, Ho TW, Bigal ME, Durham PL. Elevated saliva calcitonin gene-related peptide levels during acute migraine predict therapeutic response to rizatriptan. Headache. 2009 Oct;49(9):1258-66. doi: 10.1111/j.1526-4610.2009.01523.x.

  PMID: 19788468 BACKGROUND

• Durham PL, Cady R, Cady R. Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache. 2004 Jan;44(1):35-42; discussion 42-3. doi: 10.1111/j.1526-4610.2004.04007.x.

  PMID: 14979881 BACKGROUND

• Bruno PP, Carpino F, Carpino G, Zicari A. An overview on immune system and migraine. Eur Rev Med Pharmacol Sci. 2007 Jul-Aug;11(4):245-8.

  PMID: 17876959 BACKGROUND

• Perini F, D'Andrea G, Galloni E, Pignatelli F, Billo G, Alba S, Bussone G, Toso V. Plasma cytokine levels in migraineurs and controls. Headache. 2005 Jul-Aug;45(7):926-31. doi: 10.1111/j.1526-4610.2005.05135.x.

  PMID: 15985111 BACKGROUND

• Sarchielli P, Alberti A, Vaianella L, Pierguidi L, Floridi A, Mazzotta G, Floridi A, Gallai V. Chemokine levels in the jugular venous blood of migraine without aura patients during attacks. Headache. 2004 Nov-Dec;44(10):961-8. doi: 10.1111/j.1526-4610.2004.04189.x.

  PMID: 15546258 BACKGROUND

• Munno I, Marinaro M, Bassi A, Cassiano MA, Causarano V, Centonze V. Immunological aspects in migraine: increase of IL-10 plasma levels during attack. Headache. 2001 Sep;41(8):764-7. doi: 10.1046/j.1526-4610.2001.01140.x.

  PMID: 11576199 BACKGROUND

MeSH Terms

Interventions

Botulinum Toxins, Type A; Sodium Chloride

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Due to identified lab errors related to processing of samples for CGRP and cytokine levels, samples are currently being re-processed. Results will be posted following re-analysis of all study data related to sample values.

Results Point of Contact

• Title: Jeanne Tarrasch
• Organization: Clinvest

jtarrasch@clinvest.com

417-841-3673

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: CROSSOVER
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2010
• First Posted: February 19, 2010
• Study Start: June 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: February 12, 2013
• Results First Posted: February 17, 2012

Record last verified: 2013-02

Locations

US (2)