MigraineCGRP-RNANCT04473976
Plasma Levels of CGRP and Expression of Specific microRNAs in Blood Cells of Episodic and Chronic Migraine Subjects
An observational study of Migraine, run by IRCCS National Neurological Institute "C. Mondino" Foundation at 1 site in Italy.
Trial summary
Migraine can manifest with an episodic or chronic pattern in a continuum of disease severity. Multiple factors are associated to the transformation of the pattern form episodic to chronic. Of these, the most consistently reported is the overuse of medications (MO) for the acute treatment of attacks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Migraine
- How many people
- 55 participants
- Where
- 1 siteItaly
- Study dates
- 15 Dec 2017to 15 Jun 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Twenty-seven subjects with EM and 28 subjects with CM-MO were consecutively enrolled among patients attending the outpatient clinics of the Headache Science Centre of the IRCCS Mondino Foundation of Pavia (Italy).
Who may be able to join
- diagnosis of migraine without aura according to The International Classification Headache Disorders 3rd edition (ICHD-3) criteria;
- documented history of EM for at least 10 years before enrollment;
- negative life-time history of CM.
- diagnosis of CM and MO according to ICHD-3 criteria;
- documented pattern of stable CM in the 5 years prior to enrollment, without any remission period. This latter point was verified with a high degree of confidence combining the information obtained from the patients' history with their medical records, including their headache diaries.
Who cannot join
- headache or headache with migraine features and mild intensity (less than 4 on 0 to 10 visual analogue scale) in the 24 hours before blood sampling;
- intake of acute anti-migraine medications in the 24 hours before blood sampling.
- headache or headache with migraine features and mild intensity (less than 4 on 0 to 10 visual analogue scale) in the 24 hours before blood sampling;
- intake of acute anti-migraine medications in the 24 hours before blood sampling.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Plasma Levels of CGRP and Expression of Specific microRNAs in Blood Cells of Episodic and Chronic Migraine Subjects: Toward the Identification of a Panel of Peripheral Biomarkers of Migraine?
Migraine can manifest with an episodic or chronic pattern in a continuum of disease severity. Multiple factors are associated to the transformation of the pattern form episodic to chronic. Of these, the most consistently reported is the overuse of medications (MO) for the acute treatment of attacks. Knowledge of the mechanisms through which MO facilitates the transformation of episodic migraine (EM) into chronic migraine (CM) is very limited. In order insights into these mechanisms, the present study was aimed at identifying possible peripheral biomarkers associated to the 2 forms of migraine and to the presence of MO.
The investigators evaluated CGRP plasma levels and the expression of miR-34a-5p and miR-382-5p in peripheral blood mononuclear cells of subjects with episodic migraine (EM, n=27) and CM-MO (n=28). CM-MO group was also tested 2 months after an in-hospital detoxification protocol.
Read the detailed description
Chronic migraine (CM) is a highly disabling condition that frequently manifests as a negative evolution of episodic migraine (EM) taking place over years. In a recent meta-analysis on the predictors of migraine chronification, a number of monthly headache days >10 showed the strongest level of evidence, with depression and low household income being supported by moderate evidence. In the same meta-analysis, medication overuse (MO) was associated to the highest risk ratio in a random-effects model (RR 8.82; 95% Confidence Interval (CI), 2.88-27) but the strength of evidence was rated 'very low'due to substantial heterogeneity among studies.
It is likely that CM is the result of the dynamic interaction of multiple co-factors acting on a substrate represented by a more aggressive type of migraine. This hypothesis would explain why as many as 75% of CM subjects can spontaneously fluctuate around chronicity and episodicity. On the other hand, multiple pieces of evidence show that withdrawal from overuse medications induces a clinically meaningful improvement in a large percentage of subjects, with rates of benefit that are too high to be ascribed to a simple placebo effect.
The mechanisms underlying the negative effect of MO in migraine outcome are largely unknown. Neural mechanisms including a combination of nociceptive facilitation with weakened descending pain inhibition, associated with trigeminal hyperexcitability, may be involved. The loss of diffuse descending inhibition has been demonstrated in a preclinical model of CM with MO. In this frame, it is worth noting that the investigators have recently reported a marked derangement of the endocannabinoid system in subjects with CM and MO (CM-MO), which was more marked when compared with subjects suffering from episodic migraine (EM). Interestingly, detoxification induced in CM-MO subjects the normalization of pain thresholds paralleled by the reduction in headache frequency. Pre-clinical studies show that triptans, the specific symptomatic migraine drugs, induce a condition of hyperalgesia when administered chronically. Thus, it is possible that acute migraine medications taken in repeated episodes of pain may amplify the consequences of nociceptor activation and increase the probability of subsequent migraine attacks, together with the risk of medication overuse.
In this context of multiple concurrent causes, it seems extremely important to investigate in more depth the mechanisms that may be involved in CM and MO. Calcitonin gene-related peptide (CGRP) undoubtedly plays an important, though not exclusive, role in the generation of migraine headaches. CGRP receptors are localized in the sites involved in migraine pathogenesis. CGRP is involved in mast cell degranulation, neurogenic inflammation, and vasodilation. It has been shown that CGRP induces InterLeukin-6 (IL-6) gene expression in macrophages by upregulation of circular RNA_007893, a modulator of MicroRNA-485-5p. MicroRNAs (miRNAs) are involved in the generation and maintenance of chronic pain and several lines of evidence suggest that specific miRNAs may play a role in migraine pain. In a previous clinical study, Andersen and colleagues found an increased expression of miR-34a-5p during migraine attacks, while miR-382-5p levels increased also in the attack-free phase. In addition, the peripheral expression of miR-34a-5p decreased in the saliva of young migraineurs patients under drug treatment, thus suggesting a possible role in the prediction of therapeutic response. At present, no reliable individual biomarker of migraine and its subtypes has been identified, though multiple molecules have been proposed and supported by promising results.
In this study, the investigators assayed the plasma levels of CGRP and the expression of miRNAs in PBMCs of patients with EM and CM-MO in order to identify individual or a panel of potential biomarkers of migraine subtypes. As secondary outcome, the investigators evaluated the changes in CGRP and miRNAs levels after detoxification in the subjects with CM-MO in order to gather more insights into the mechanisms that are involved in the improvement of migraine pattern following the withdrawal of the overused medications.
This is a cross-sectional observational controlled study with 2 groups (EM and CM-MO), integrated with a prospective open label interventional trial to assess the effect of detoxification in the CM-MO group on the biomarkers of interest. Samples were labeled with numerical codes and all biochemical determinations were performed by researchers who were blind to the diagnosis.
At baseline (Day 0), all patients underwent a visit with a neurologist of the Headache Science Centre during which clinical/demographical data were recorded and inclusion/exclusion criteria were checked. If the criteria were met, subjects underwent peripheral venipuncture for the evaluation of CGRP, miR-382-5p, and miR-34a-5p levels.
Patients with CM-MO were hospitalized for a 7-day standardized detoxification protocol, consisting in abrupt withdrawal of overused drugs associated to intravenous therapy twice daily (08:00 a.m. and 4:00 p.m.) with isotonic 0.9% Sodium Chloride (NaCl) saline 500 ml + cyanocobalamin 2500 mcg + folic acid 0.70 mg + nicotinamide 12 mg + ascorbic acid 150 mg + sodic glutathione 600 mg + delorazepam 0.5 mg. Two months after hospital discharge (Day 1), the CM-MO patients returned for a follow-up visit, during which clinical data were recorded and a second venous blood sample obtained from their ante-cubital vein.
- Conditions
- Migraine
- Keywords
- Migraine, CGRP, MicroRNA, Overuse of medications
- Medical subject headings
- Migraine Disorders
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma levels of CGRP
In order to identify individual or a panel of potential biomarkers of migraine subtypes
Measured: Day 0 at the enrolment
Expression of miRNAs in PBMCs
In order to identify individual or a panel of potential biomarkers of migraine subtypes
Measured: Day 0 at the enrolment
Secondary outcomes (2)
Changes in CGRP levels
In the subjects with CM-MO after detoxification in order to gather more insights into the mechanisms that are involved in the improvement of migraine pattern following the withdrawal of the overused medications.
Measured: Day1 - Two months after Day 0
Changes in miRNAs levels
In the subjects with CM-MO after detoxification in order to gather more insights into the mechanisms that are involved in the improvement of migraine pattern following the withdrawal of the overused medications.
Measured: Day 1 - Two months after Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2020
- Study start15 Dec 2017
- Primary completion15 Apr 2019
- Study completion15 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for 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
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pavia
- Responsible party
- Sponsor
- Investigators
- Cristina Tassorelli, Prof, Principal investigator, IRCCS Mondino Foundation, Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04473976
- Sponsor's protocol ID
- CGRP-microRNA2020
- Acronym
- CGRP-RNA
- Status last verified
- Jul 2020
- First submitted
- 13 Jul 2020
- Last updated
- 20 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Diener HC, Tassorelli C, Dodick DW, Silberstein SD, Lipton RB, Ashina M, Becker WJ, Ferrari MD, Goadsby PJ, Pozo-Rosich P, Wang SJ, Mandrekar J; International Headache Society Clinical Trials Standing Committee. Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition. Cephalalgia. 2019 May;39(6):687-710. doi: 10.1177/0333102419828967. Epub 2019 Feb 26.
PubMed 30806518Xu J, Kong F, Buse DC. Predictors of episodic migraine transformation to chronic migraine: A systematic review and meta-analysis of observational cohort studies. Cephalalgia. 2020 Apr;40(5):503-516. doi: 10.1177/0333102419883355. Epub 2019 Oct 21.
PubMed 31635478Serrano D, Lipton RB, Scher AI, Reed ML, Stewart WBF, Adams AM, Buse DC. Fluctuations in episodic and chronic migraine status over the course of 1 year: implications for diagnosis, treatment and clinical trial design. J Headache Pain. 2017 Oct 4;18(1):101. doi: 10.1186/s10194-017-0787-1.
PubMed 28980171Tassorelli C, Jensen R, Allena M, De Icco R, Sances G, Katsarava Z, Lainez M, Leston J, Fadic R, Spadafora S, Pagani M, Nappi G; the COMOESTAS Consortium. A consensus protocol for the management of medication-overuse headache: Evaluation in a multicentric, multinational study. Cephalalgia. 2014 Aug;34(9):645-655. doi: 10.1177/0333102414521508. Epub 2014 Feb 20.
PubMed 24558185Rossi P, Faroni JV, Tassorelli C, Nappi G. Advice alone versus structured detoxification programmes for complicated medication overuse headache (MOH): a prospective, randomized, open-label trial. J Headache Pain. 2013 Feb 8;14(1):10. doi: 10.1186/1129-2377-14-10.
PubMed 23565591Meng ID, Dodick D, Ossipov MH, Porreca F. Pathophysiology of medication overuse headache: insights and hypotheses from preclinical studies. Cephalalgia. 2011 May;31(7):851-60. doi: 10.1177/0333102411402367. Epub 2011 Mar 28.
PubMed 21444643Diener HC, Dodick D, Evers S, Holle D, Jensen RH, Lipton RB, Porreca F, Silberstein S, Schwedt T. Pathophysiology, prevention, and treatment of medication overuse headache. Lancet Neurol. 2019 Sep;18(9):891-902. doi: 10.1016/S1474-4422(19)30146-2. Epub 2019 Jun 4.
PubMed 31174999De Felice M, Ossipov MH, Porreca F. Persistent medication-induced neural adaptations, descending facilitation, and medication overuse headache. Curr Opin Neurol. 2011 Jun;24(3):193-6. doi: 10.1097/WCO.0b013e328346af25.
PubMed 21467931Munksgaard SB, Bendtsen L, Jensen RH. Modulation of central sensitisation by detoxification in MOH: results of a 12-month detoxification study. Cephalalgia. 2013 May;33(7):444-53. doi: 10.1177/0333102412475235. Epub 2013 Feb 21.
PubMed 23431023De Felice M, Ossipov MH, Wang R, Lai J, Chichorro J, Meng I, Dodick DW, Vanderah TW, Dussor G, Porreca F. Triptan-induced latent sensitization: a possible basis for medication overuse headache. Ann Neurol. 2010 Mar;67(3):325-37. doi: 10.1002/ana.21897.
PubMed 20373344Lambru G, Andreou AP, Guglielmetti M, Martelletti P. Emerging drugs for migraine treatment: an update. Expert Opin Emerg Drugs. 2018 Dec;23(4):301-318. doi: 10.1080/14728214.2018.1552939. Epub 2018 Nov 30.
PubMed 30484333Deng T, Yang L, Zheng Z, Li Y, Ren W, Wu C, Guo L. Calcitonin gene-related peptide induces IL-6 expression in RAW264.7 macrophages mediated by mmu_circRNA_007893. Mol Med Rep. 2017 Dec;16(6):9367-9374. doi: 10.3892/mmr.2017.7779. Epub 2017 Oct 12.
PubMed 29039515Gallelli L, Siniscalchi A, Carotenuto M, Caroleo MC, Cione E, Guidetti V. microRNAs-based Predictor Factor in Patients with Migraine-ischemic Stroke. Microrna. 2017;6(1):17-21. doi: 10.2174/2211536606666170104130101.
PubMed 28056747Ferroni P, Barbanti P, Spila A, Fratangeli F, Aurilia C, Fofi L, Egeo G, Guadagni F. Circulating Biomarkers in Migraine: New Opportunities for Precision Medicine. Curr Med Chem. 2019;26(34):6191-6206. doi: 10.2174/0929867325666180622122938.
PubMed 29932027Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.
PubMed 29368949
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma Levels of CGRP and Expression of Specific microRNAs in Blood Cells of Episodic and Chronic Migraine Subjects: Toward the Identification of a Panel of Peripheral Biomarkers of Migraine?
- ClinicalTrials.gov ID
- NCT04473976
- Acronym / sponsor ID
- CGRP-RNA / CGRP-microRNA2020
- Conditions
- Migraine
- Keywords
- Migraine, CGRP, MicroRNA, Overuse of medications
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" FoundationUniversity, hospital or other
- Collaborators
- University of Pavia
- Study start
- 15 Dec 2017 (actual)
- Primary completion
- 15 Apr 2019 (actual)
- Study completion
- 15 Jun 2019 (actual)
- First posted
- 16 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Migraine can manifest with an episodic or chronic pattern in a continuum of disease severity. Multiple factors are associated to the transformation of the pattern form episodic to chronic. Of these, the most consistently reported is the overuse of medications (MO) for the acute treatment of attacks. Knowledge of the mechanisms through which MO facilitates the transformation of episodic migraine (EM) into chronic migraine (CM) is very limited. In order insights into these mechanisms, the present study was aimed at identifying possible peripheral biomarkers associated to the 2 forms of migraine and to the presence of MO.
The investigators evaluated CGRP plasma levels and the expression of miR-34a-5p and miR-382-5p in peripheral blood mononuclear cells of subjects with episodic migraine (EM, n=27) and CM-MO (n=28). CM-MO group was also tested 2 months after an in-hospital detoxification protocol.
Detailed description
Chronic migraine (CM) is a highly disabling condition that frequently manifests as a negative evolution of episodic migraine (EM) taking place over years. In a recent meta-analysis on the predictors of migraine chronification, a number of monthly headache days >10 showed the strongest level of evidence, with depression and low household income being supported by moderate evidence. In the same meta-analysis, medication overuse (MO) was associated to the highest risk ratio in a random-effects model (RR 8.82; 95% Confidence Interval (CI), 2.88-27) but the strength of evidence was rated 'very low'due to substantial heterogeneity among studies.
It is likely that CM is the result of the dynamic interaction of multiple co-factors acting on a substrate represented by a more aggressive type of migraine. This hypothesis would explain why as many as 75% of CM subjects can spontaneously fluctuate around chronicity and episodicity. On the other hand, multiple pieces of evidence show that withdrawal from overuse medications induces a clinically meaningful improvement in a large percentage of subjects, with rates of benefit that are too high to be ascribed to a simple placebo effect.
The mechanisms underlying the negative effect of MO in migraine outcome are largely unknown. Neural mechanisms including a combination of nociceptive facilitation with weakened descending pain inhibition, associated with trigeminal hyperexcitability, may be involved. The loss of diffuse descending inhibition has been demonstrated in a preclinical model of CM with MO. In this frame, it is worth noting that the investigators have recently reported a marked derangement of the endocannabinoid system in subjects with CM and MO (CM-MO), which was more marked when compared with subjects suffering from episodic migraine (EM). Interestingly, detoxification induced in CM-MO subjects the normalization of pain thresholds paralleled by the reduction in headache frequency. Pre-clinical studies show that triptans, the specific symptomatic migraine drugs, induce a condition of hyperalgesia when administered chronically. Thus, it is possible that acute migraine medications taken in repeated episodes of pain may amplify the consequences of nociceptor activation and increase the probability of subsequent migraine attacks, together with the risk of medication overuse.
In this context of multiple concurrent causes, it seems extremely important to investigate in more depth the mechanisms that may be involved in CM and MO. Calcitonin gene-related peptide (CGRP) undoubtedly plays an important, though not exclusive, role in the generation of migraine headaches. CGRP receptors are localized in the sites involved in migraine pathogenesis. CGRP is involved in mast cell degranulation, neurogenic inflammation, and vasodilation. It has been shown that CGRP induces InterLeukin-6 (IL-6) gene expression in macrophages by upregulation of circular RNA_007893, a modulator of MicroRNA-485-5p. MicroRNAs (miRNAs) are involved in the generation and maintenance of chronic pain and several lines of evidence suggest that specific miRNAs may play a role in migraine pain. In a previous clinical study, Andersen and colleagues found an increased expression of miR-34a-5p during migraine attacks, while miR-382-5p levels increased also in the attack-free phase. In addition, the peripheral expression of miR-34a-5p decreased in the saliva of young migraineurs patients under drug treatment, thus suggesting a possible role in the prediction of therapeutic response. At present, no reliable individual biomarker of migraine and its subtypes has been identified, though multiple molecules have been proposed and supported by promising results.
In this study, the investigators assayed the plasma levels of CGRP and the expression of miRNAs in PBMCs of patients with EM and CM-MO in order to identify individual or a panel of potential biomarkers of migraine subtypes. As secondary outcome, the investigators evaluated the changes in CGRP and miRNAs levels after detoxification in the subjects with CM-MO in order to gather more insights into the mechanisms that are involved in the improvement of migraine pattern following the withdrawal of the overused medications.
This is a cross-sectional observational controlled study with 2 groups (EM and CM-MO), integrated with a prospective open label interventional trial to assess the effect of detoxification in the CM-MO group on the biomarkers of interest. Samples were labeled with numerical codes and all biochemical determinations were performed by researchers who were blind to the diagnosis.
At baseline (Day 0), all patients underwent a visit with a neurologist of the Headache Science Centre during which clinical/demographical data were recorded and inclusion/exclusion criteria were checked. If the criteria were met, subjects underwent peripheral venipuncture for the evaluation of CGRP, miR-382-5p, and miR-34a-5p levels.
Patients with CM-MO were hospitalized for a 7-day standardized detoxification protocol, consisting in abrupt withdrawal of overused drugs associated to intravenous therapy twice daily (08:00 a.m. and 4:00 p.m.) with isotonic 0.9% Sodium Chloride (NaCl) saline 500 ml + cyanocobalamin 2500 mcg + folic acid 0.70 mg + nicotinamide 12 mg + ascorbic acid 150 mg + sodic glutathione 600 mg + delorazepam 0.5 mg. Two months after hospital discharge (Day 1), the CM-MO patients returned for a follow-up visit, during which clinical data were recorded and a second venous blood sample obtained from their ante-cubital vein.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Twenty-seven subjects with EM and 28 subjects with CM-MO were consecutively enrolled among patients attending the outpatient clinics of the Headache Science Centre of the IRCCS Mondino Foundation of Pavia (Italy).
Key inclusion criteria (5 listed)
- diagnosis of migraine without aura according to The International Classification Headache Disorders 3rd edition (ICHD-3) criteria;
- documented history of EM for at least 10 years before enrollment;
- negative life-time history of CM.
- diagnosis of CM and MO according to ICHD-3 criteria;
- documented pattern of stable CM in the 5 years prior to enrollment, without any remission period. This latter point was verified with a high degree of confidence combining the information obtained from the patients' history with their medical records, including their headache diaries.
Key exclusion criteria (4 listed)
- headache or headache with migraine features and mild intensity (less than 4 on 0 to 10 visual analogue scale) in the 24 hours before blood sampling;
- intake of acute anti-migraine medications in the 24 hours before blood sampling.
- headache or headache with migraine features and mild intensity (less than 4 on 0 to 10 visual analogue scale) in the 24 hours before blood sampling;
- intake of acute anti-migraine medications in the 24 hours before blood sampling.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Plasma levels of CGRP
Time frame: Day 0 at the enrolment
In order to identify individual or a panel of potential biomarkers of migraine subtypes
Expression of miRNAs in PBMCs
Time frame: Day 0 at the enrolment
In order to identify individual or a panel of potential biomarkers of migraine subtypes
2 secondary outcomes
Changes in CGRP levels
Time frame: Day1 - Two months after Day 0
Changes in miRNAs levels
Time frame: Day 1 - Two months after Day 0
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2020.
- Background: PubMed 30806518Diener HC, Tassorelli C, Dodick DW, Silberstein SD, Lipton RB, Ashina M, Becker WJ, Ferrari MD, Goadsby PJ, Pozo-Rosich P, Wang SJ, Mandrekar J; International Headache Society Clinical Trials Standing Committee. Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition. Cephalalgia. 2019 May;39(6):687-710. doi: 10.1177/0333102419828967. Epub 2019 Feb 26.
- Background: PubMed 31635478Xu J, Kong F, Buse DC. Predictors of episodic migraine transformation to chronic migraine: A systematic review and meta-analysis of observational cohort studies. Cephalalgia. 2020 Apr;40(5):503-516. doi: 10.1177/0333102419883355. Epub 2019 Oct 21.
- Background: PubMed 28980171Serrano D, Lipton RB, Scher AI, Reed ML, Stewart WBF, Adams AM, Buse DC. Fluctuations in episodic and chronic migraine status over the course of 1 year: implications for diagnosis, treatment and clinical trial design. J Headache Pain. 2017 Oct 4;18(1):101. doi: 10.1186/s10194-017-0787-1.
- Background: PubMed 24558185Tassorelli C, Jensen R, Allena M, De Icco R, Sances G, Katsarava Z, Lainez M, Leston J, Fadic R, Spadafora S, Pagani M, Nappi G; the COMOESTAS Consortium. A consensus protocol for the management of medication-overuse headache: Evaluation in a multicentric, multinational study. Cephalalgia. 2014 Aug;34(9):645-655. doi: 10.1177/0333102414521508. Epub 2014 Feb 20.
- Background: PubMed 23565591Rossi P, Faroni JV, Tassorelli C, Nappi G. Advice alone versus structured detoxification programmes for complicated medication overuse headache (MOH): a prospective, randomized, open-label trial. J Headache Pain. 2013 Feb 8;14(1):10. doi: 10.1186/1129-2377-14-10.
- Background: PubMed 21444643Meng ID, Dodick D, Ossipov MH, Porreca F. Pathophysiology of medication overuse headache: insights and hypotheses from preclinical studies. Cephalalgia. 2011 May;31(7):851-60. doi: 10.1177/0333102411402367. Epub 2011 Mar 28.
- Background: PubMed 31174999Diener HC, Dodick D, Evers S, Holle D, Jensen RH, Lipton RB, Porreca F, Silberstein S, Schwedt T. Pathophysiology, prevention, and treatment of medication overuse headache. Lancet Neurol. 2019 Sep;18(9):891-902. doi: 10.1016/S1474-4422(19)30146-2. Epub 2019 Jun 4.
- Background: PubMed 21467931De Felice M, Ossipov MH, Porreca F. Persistent medication-induced neural adaptations, descending facilitation, and medication overuse headache. Curr Opin Neurol. 2011 Jun;24(3):193-6. doi: 10.1097/WCO.0b013e328346af25.
- Background: PubMed 23431023Munksgaard SB, Bendtsen L, Jensen RH. Modulation of central sensitisation by detoxification in MOH: results of a 12-month detoxification study. Cephalalgia. 2013 May;33(7):444-53. doi: 10.1177/0333102412475235. Epub 2013 Feb 21.
- Background: PubMed 20373344De Felice M, Ossipov MH, Wang R, Lai J, Chichorro J, Meng I, Dodick DW, Vanderah TW, Dussor G, Porreca F. Triptan-induced latent sensitization: a possible basis for medication overuse headache. Ann Neurol. 2010 Mar;67(3):325-37. doi: 10.1002/ana.21897.
- Background: PubMed 30484333Lambru G, Andreou AP, Guglielmetti M, Martelletti P. Emerging drugs for migraine treatment: an update. Expert Opin Emerg Drugs. 2018 Dec;23(4):301-318. doi: 10.1080/14728214.2018.1552939. Epub 2018 Nov 30.
- Background: PubMed 29039515Deng T, Yang L, Zheng Z, Li Y, Ren W, Wu C, Guo L. Calcitonin gene-related peptide induces IL-6 expression in RAW264.7 macrophages mediated by mmu_circRNA_007893. Mol Med Rep. 2017 Dec;16(6):9367-9374. doi: 10.3892/mmr.2017.7779. Epub 2017 Oct 12.
- Individual participant dataSharing planned: No
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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.
Cristina Tassorelli, Prof principal investigator
IRCCS Mondino Foundation, Pavia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Migraine, run by IRCCS National Neurological Institute "C. Mondino" Foundation at 1 site in Italy.
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 5 inclusion and 4 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 20 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Plasma levels of CGRP (time frame: Day 0 at the enrolment). The study lists 2 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 NCT04473976, which also lists 26 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 20 Jul 2020.