NCT04324710

Brief Summary

Preclinical and clinical evidence suggests a role for the dysregulation of endocannabinoid system (ES) in migraine pain, particularly in subjects with chronic migraine. The gene expression of ES components were assayed in peripheral blood mononuclear cells (PBMCs) of patients with episodic migraine (EM), chronic migraine with medication overuse (CM-MO) and age-matched healthy controls (CT). It was evaluated the protein expression of cannabinoid receptors (CB) 1 and 2 as well as DNA methylation changes in genes involved in ES components.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
75

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Dec 2017

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 12, 2017

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2019

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

March 25, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 27, 2020

Completed
Last Updated

March 27, 2020

Status Verified

March 1, 2020

Enrollment Period

2.1 years

First QC Date

March 25, 2020

Last Update Submit

March 25, 2020

Conditions

Chronic Migraine

Keywords

EndocannabinoidsMedication overusePeripheral blood mononuclear cells

Outcome Measures

Primary Outcomes (8)

  • CB1 (endocannabinoid receptor) protein expression

    CB1 protein expression in the peripheral blood mononuclear cells (PBMCs)

    At the time of enrollment

  • CB2 (endocannabinoid receptor) protein expression

    CB2 protein expression in the peripheral blood mononuclear cells (PBMCs)

    At the time of enrollment

  • Gene Expression of the CB receptors

    Gene expression of the endocannabinoid receptors in the peripheral blood mononuclear cells ( PBMCs)

    At the time of enrollment

  • Gene Expression of the fatty acid amide hydrolase (FAAH)

    Gene expression of the FAAH in the peripheral blood mononuclear cells ( PBMCs)

    At the time of enrollment

  • Gene Expression of the N-acylphosphatidylethanolamide-phospholipase D (NAPE-PLD)

    Gene expression of the NAPE-PLD in the peripheral blood mononuclear cells ( PBMCs)

    At the time of enrollment

  • Gene Expression of the diacylglycerol lipase (DAGL)

    Gene expression of the DAGL in the peripheral blood mononuclear cells ( PBMCs)

    At the time of enrollment

  • Gene Expression of the monoacylglycerol lipase (MAGL).

    Gene expression of the MAGL in the peripheral blood mononuclear cells ( PBMCs)

    At the time of enrollment

  • DNA methylation of endocannabinoid system (ES) components

    DNA methylation in the regulation of ES gene transcription

    At the time of enrollment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Patients with episodic migraine (EM), chronic migraine with medication overuse (CM-MO) and age-matched healthy controls (CT).

You may qualify if:

  • satisfaction of the diagnostic criteria for migraine without aura according to the International Headache Classification 3rd edition (ICHD-3);
  • an episodic pattern of migraine for at least 10 years without any period of chronification.

You may not qualify if:

  • any systemic diseases, psychiatric disorders or any other clinically significant conditions.
  • satisfaction of the ICHD-3 diagnostic criteria for chronic migraine and for one of the subtypes of medication overuse headache;
  • a history of stable chronification for at least 5 years.
  • any systemic diseases, psychiatric disorders or any other clinically significant conditions.
  • no history of migraine or other primary headaches;
  • Infrequent tension-type headache episodes.
  • any systemic diseases, psychiatric disorders or any other clinically significant conditions;
  • any type of painkiller in the 24 hours prior to the blood sampling.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ircss Mondino Foundation

Pavia, 27100, Italy

Location

Related Publications (12)

  • Basavarajappa BS, Nixon RA, Arancio O. Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration. Mini Rev Med Chem. 2009 Apr;9(4):448-62. doi: 10.2174/138955709787847921.

    PMID: 19356123BACKGROUND

  • Greco R, Demartini C, Zanaboni AM, Piomelli D, Tassorelli C. Endocannabinoid System and Migraine Pain: An Update. Front Neurosci. 2018 Mar 19;12:172. doi: 10.3389/fnins.2018.00172. eCollection 2018.

    PMID: 29615860BACKGROUND

  • Greco R, Demartini C, Zanaboni AM, Tumelero E, Reggiani A, Misto A, Piomelli D, Tassorelli C. FAAH inhibition as a preventive treatment for migraine: A pre-clinical study. Neurobiol Dis. 2020 Feb;134:104624. doi: 10.1016/j.nbd.2019.104624. Epub 2019 Oct 17.

    PMID: 31629892BACKGROUND

  • La Porta C, Bura SA, Llorente-Onaindia J, Pastor A, Navarrete F, Garcia-Gutierrez MS, De la Torre R, Manzanares J, Monfort J, Maldonado R. Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain. Pain. 2015 Oct;156(10):2001-2012. doi: 10.1097/j.pain.0000000000000260.

    PMID: 26067584BACKGROUND

  • Centonze D, Battistini L, Maccarrone M. The endocannabinoid system in peripheral lymphocytes as a mirror of neuroinflammatory diseases. Curr Pharm Des. 2008;14(23):2370-42. doi: 10.2174/138161208785740018.

    PMID: 18781987BACKGROUND

  • Sarchielli P, Pini LA, Coppola F, Rossi C, Baldi A, Mancini ML, Calabresi P. Endocannabinoids in chronic migraine: CSF findings suggest a system failure. Neuropsychopharmacology. 2007 Jun;32(6):1384-90. doi: 10.1038/sj.npp.1301246. Epub 2006 Nov 22.

    PMID: 17119542BACKGROUND

  • Arosio B, Bulbarelli A, Bastias Candia S, Lonati E, Mastronardi L, Romualdi P, Candeletti S, Gussago C, Galimberti D, Scarpini E, Dell'Osso B, Altamura C, MacCarrone M, Bergamaschini L, D'Addario C, Mari D. Pin1 contribution to Alzheimer's disease: transcriptional and epigenetic mechanisms in patients with late-onset Alzheimer's disease. Neurodegener Dis. 2012;10(1-4):207-11. doi: 10.1159/000333799. Epub 2012 Jan 17.

    PMID: 22261503BACKGROUND

  • Van der Schueren BJ, Van Laere K, Gerard N, Bormans G, De Hoon JN. Interictal type 1 cannabinoid receptor binding is increased in female migraine patients. Headache. 2012 Mar;52(3):433-40. doi: 10.1111/j.1526-4610.2011.02030.x. Epub 2011 Nov 11.

    PMID: 22077199BACKGROUND

  • Perrotta A, Arce-Leal N, Tassorelli C, Gasperi V, Sances G, Blandini F, Serrao M, Bolla M, Pierelli F, Nappi G, Maccarrone M, Sandrini G. Acute reduction of anandamide-hydrolase (FAAH) activity is coupled with a reduction of nociceptive pathways facilitation in medication-overuse headache subjects after withdrawal treatment. Headache. 2012 Oct;52(9):1350-61. doi: 10.1111/j.1526-4610.2012.02170.x. Epub 2012 Jun 1.

    PMID: 22670561BACKGROUND

  • Frieling H, Albrecht H, Jedtberg S, Gozner A, Lenz B, Wilhelm J, Hillemacher T, de Zwaan M, Kornhuber J, Bleich S. Elevated cannabinoid 1 receptor mRNA is linked to eating disorder related behavior and attitudes in females with eating disorders. Psychoneuroendocrinology. 2009 May;34(4):620-4. doi: 10.1016/j.psyneuen.2008.10.014. Epub 2008 Nov 28.

    PMID: 19046818BACKGROUND

  • Greco R, Bandiera T, Mangione AS, Demartini C, Siani F, Nappi G, Sandrini G, Guijarro A, Armirotti A, Piomelli D, Tassorelli C. Effects of peripheral FAAH blockade on NTG-induced hyperalgesia--evaluation of URB937 in an animal model of migraine. Cephalalgia. 2015 Oct;35(12):1065-76. doi: 10.1177/0333102414566862. Epub 2015 Jan 21.

    PMID: 25608877BACKGROUND

  • Greco R, Gasperi V, Sandrini G, Bagetta G, Nappi G, Maccarrone M, Tassorelli C. Alterations of the endocannabinoid system in an animal model of migraine: evaluation in cerebral areas of rat. Cephalalgia. 2010 Mar;30(3):296-302. doi: 10.1111/j.1468-2982.2009.01924.x. Epub 2010 Feb 1.

    PMID: 19515121BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Since PBMCs contain the full complement of epigenetic enzymes found in most tissues, the investigators evaluated the role of DNA methylation in the regulation of ES gene transcription in all the enrolled subjects. DNA was extracted from whole blood using QIAmp DNA Blood Mini Kit and its concentration was determined by NanoDrop quantification. Arrays preparation and data analysis were performed by Genomix4Life srl. High-quality DNA (500 ng) was bisulfite converted using EZ DNA methylation kit. Bisulfite converted DNA (200ng) was used for analysis of whole-genome methylation, using the HumanMethylation 450 K BeadChip, which contains 485 577 probes covering 21 231 (99%) RefSeq genes.

MeSH Terms

Conditions

Prescription Drug Overuse

Condition Hierarchy (Ancestors)

Prescription Drug MisuseDrug MisuseSubstance-Related DisordersChemically-Induced DisordersMental Disorders

Study Officials

  • Cristina Tassorelli, MD

    IRCCS MONDINO FOUNDATION

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 25, 2020

First Posted

March 27, 2020

Study Start

December 12, 2017

Primary Completion

December 31, 2019

Study Completion

December 31, 2019

Last Updated

March 27, 2020

Record last verified: 2020-03

Locations

IT(1)