- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT01071096
Calcitonin Gene-related Peptide Levels in Chronic Migraine
Calcitonin Gene-related Peptide (CGRP) Levels in the Pathogenesis of Chronic Migraine
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 .
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
This double-blind study will evaluate reduction in number of headache days following treatment with OnabotulinumtoxinA versus Saline. Additionally, CGRP levels in saliva will be correlated with a reduction in headache attacks.
At Visit 1, eligible subjects will be randomized 1:1 to receive injections of OnabotulinumtoxinA or Saline in an identical manner. Subjects will collect 3 saliva samples during each month of the 7 month study: 1 collection at Baseline headache level, 1 collection at onset of headache that is one degree worse than Baseline level that will be treated with acute therapy, and 1 collection at 2 hours following treatment. Subjects will document headache and headache symptoms in a daily diary and return to the clinic with diary and saliva samples at monthly visits.
Following 4 months (including a 1 month washout after Visit 4), subjects will return at Visit 5 and receive cross-over injections. Subjects randomized to OnabotulinumtoxinA at Visit 1 will receive injections of Saline. Subjects randomized to saline at Visit 1 will receive injections of OnabotulinumtoxinA. Subjects will document headache and headache symptoms in a daily diary and return to the clinic with diary and saliva samples at monthly visits.
At Visit 8, 3 months following re-injection at Visit 5, subjects will exit the study.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 4
Contatti e Sedi
Luoghi di studio
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Missouri
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Springfield, Missouri, Stati Uniti, 65807
- Clinvest
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New York
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Plainview, New York, Stati Uniti, 11803
- Island Neurological Associates, P.C.
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione incrociata
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Comparatore attivo: OnabotulinumtoxinA
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.
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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.
Altri nomi:
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Comparatore placebo: Saline
155 U Saline administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas.
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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.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7.
Lasso di tempo: Baseline (collected historically at screening) versus (vs.) Month (Mo) 1, Mo 2, Mo 3, Mo 4, Mo 5, Mo 6, and Mo 7
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Baseline number of headache days per month collected historically at screening.
Post-treatment number of headache days collected per month via diary.
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Baseline (collected historically at screening) versus (vs.) Month (Mo) 1, Mo 2, Mo 3, Mo 4, Mo 5, Mo 6, and Mo 7
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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).
Lasso di tempo: 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
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Baseline number of headache days per month collected historically at screening.
Post-treatment number of headache days collected per month via diary.
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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
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP)
Lasso di tempo: Baseline levels collected for OnabotulinumtoxinA and Saline treatment during Months 1 through 7
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CGRP Level collected each month when subject did not have a headache or was at lowest pain level of headache that month.
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Baseline levels collected for OnabotulinumtoxinA and Saline treatment during Months 1 through 7
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Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline
Lasso di tempo: For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3
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Saliva samples collected at Baseline (at no headache or lowest level of headache), at headache attack directly before taking rescue medication and 2 hours after treating with rescue medication.
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For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3
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Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders
Lasso di tempo: 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
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Only cytokines with a mean densimetric value 1.65 times the background grey value in a minimum of 3 patients were considered detectable.
These are reported below.
Values normalized to positive control array spots after background subtraction: C5/C5a, CD40 Ligand, Granulocyte Colony Stimulating Factor (G-CSF), Growth Regulated Oncogene(GRO)-alpha, Soluble Intercellular Adhesion Molecule (sICAM)-1, Interferon gamma (IFN-y), Interleukin(IL)-1alpha, 1beta, 1ra, 8, 16, 17E, & 23, Interferon Gamma-Induced Protein 10 (IP-10), Interferon-inducible T cell alpha chemoattractant (I-TAC), Macrophage Migration Inhibitory Factor (MIF), Serpin E1, and Regulated Upon Activation Normal T-cell Expressed (RANTES)
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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
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Collaboratori e investigatori
Sponsor
Collaboratori
Pubblicazioni e link utili
Pubblicazioni generali
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie del cervello
- Malattie del sistema nervoso centrale
- Malattie del sistema nervoso
- Disturbi della cefalea, primaria
- Disturbi della cefalea
- Disturbi dell'emicrania
- Effetti fisiologici delle droghe
- Agenti neurotrasmettitori
- Meccanismi molecolari dell'azione farmacologica
- Agenti del sistema nervoso periferico
- Agenti colinergici
- Modulatori di trasporto a membrana
- Inibitori del rilascio di acetilcolina
- Agenti neuromuscolari
- Tossine botuliniche
- Tossine botuliniche, tipo A
- abobotulinumtoxin A
Altri numeri di identificazione dello studio
- 10-001AL
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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