Role of Specific microRNAs in Cluster Headache

NCT06503328 | Recruiting

• 1 other identifier: miRNA - CH
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Cluster headache (CH) is a primary headache included in the trigeminal autonomic cephalalgias (TACs) according to the International Calssification of Headache Disorder, Third Edition. CH is characterized by a multifaceted and incompletely understood pathophysiology. Recent experimental evidence has increasingly emphasized the role of specific microRNAs (miRNAs) in the pathophysiology of primary headaches, including migraine. In a recent study, we observed an upregulation in the gene expression of two miRNAs, miR-382-5p and miR-34a-5p, in peripheral blood mononuclear cells (PBMCs) of subjects with chronic migraine (CM). These miRNAs are involved in inflammation modulation and the release of γ-aminobutyric acid (GABA). Notably, this upregulation correlated with the migraine phenotype and its severity. Several neuropeptides have been established to play an active role in CH. Studies by the Danish group have demonstrated that intravenous administration of CGRP, PACAP, or VIP can induce CH attacks in at least 50% of participants in the active phase of the disease. However, no data currently exists regarding the potential involvement of miRNAs in CH. Given this context, the primary aim of this study is to investigate the gene expression of specific miRNAs (miR-382-5p, miR-34a-5p, and miR-155) in PBMCs and plasma levels of neuropeptides (CGRP, PACAP, VIP) in subjects with episodic CH in the active phase (eCH-act), episodic CH in the remission phase (eCH-rem), chronic CH (cCH), and healthy control subjects (HCs).

Conditions

Cluster Headache

Keywords

MicroRNA; miR-34a-5p; miR-155; miR-382-5p; Peripheral blood mononuclear cells; CGRP; PACAP; VIP; Headache; Migraine

Outcome Measures

Primary Outcomes (1)

• PBMCs gene expression of miR-382-5p

  miR-382-5p gene expression in PBMCs will be evaluated by real-time reverse transcription (RT-PCR). This assessment will be then normalized with U6 (a type of small nuclear RNA used as housekeeping gene) and expressed as Relative Quantification (RQ).

  Single evaluation at study visit - baseline (T0)

Secondary Outcomes (3)

• PBMCs gene expression of miR-34a-5p and miR-155

  Single evaluation at study visit - baseline (T0)

• Plasma levels of CGRP alpha, PACAP and VIP

  Single evaluation at study visit - baseline (T0)

• Score of MIDAS, HIT-6, and CHIQ

  Single evaluation at study visit - baseline (T0)

Study Arms (3)

Healthy Controls

Healthy subjects without present or past history of headache according to ICHD-III criteria.

Episodic Cluster Headache

Patients with a diagnosis of "3.1.1 Episodic Cluster Headache", according to ICHD-III criteria.

Chronic Cluster Headache

Patients with a diagnosis of "3.1.2 Chronic Cluster Headache", according to ICHD-III criteria.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

We aim to enroll a representative population of patients affected by eCH in the active phase and in the remission phases and cCH. All patients will be consecutively enrolled among those attending the clinics of the Headache Science Center of the IRCCS Mondino Foundation of Pavia (Italy). A set of healthy controls, without a present or past diagnosis primary or secondary headaches, will be enrolled as control group.

You may qualify if:

• age between \>18 and \<65 years

You may not qualify if:

• diagnosis of primary and/or secondary headache according to ICHD-III criteria (only diagnosis of sporadic tension type headache is allowed)
• diagnosis of neurological disorders
• diagnosis of medical conditions considered clinically relevant by the researcher
• pregnant and lactating women
• taking NSAIDs, triptans or opiates in the previous 24 hours
• Episodic Cluster Headache
• diagnosis of Episodic Cluster Headache according to ICHD-III criteria (at least 1 year at screening)
• age between \>18 and \<65 years of both genders
• concomitant diagnosis of other primary and/or secondary headache according to ICHD-III criteria (only diagnosis of sporadic tension headache is allowed)
• diagnosis of other neurological disorders
• diagnosis of medical conditions considered clinically relevant by the researcher
• diagnosis of chronic pain syndrome of any nature
• pregnant and lactating women
• use of substances of abuse
• Chronic Cluster Headache

Sponsors & Collaborators

• IRCCS National Neurological Institute "C. Mondino" Foundation: lead

Study Sites (1)

IRCCS Mondino Foundation

Pavia, 27100, Italy

RECRUITING

Related Publications (8)

• Headache 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.

  PMID: 29368949 BACKGROUND

• Ahmad L, Demartini C, Corrado M, et al. Expression of Selected microRNAs in Migraine: A New Class of Possible Biomarkers of Disease? Processes 2021; 9: 2199.

  BACKGROUND

• Greco R, De Icco R, Demartini C, Zanaboni AM, Tumelero E, Sances G, Allena M, Tassorelli C. Plasma levels of CGRP and expression of specific microRNAs in blood cells of episodic and chronic migraine subjects: towards the identification of a panel of peripheral biomarkers of migraine? J Headache Pain. 2020 Oct 16;21(1):122. doi: 10.1186/s10194-020-01189-0.

  PMID: 33066724 BACKGROUND

• Welch KM, Chabi E, Bartosh K, Achar VS, Meyer JS. Cerebrospinal fluid gamma aminobutyric acid levels in migraine. Br Med J. 1975 Aug 30;3(5982):516-7. doi: 10.1136/bmj.3.5982.516.

  PMID: 1164613 BACKGROUND

• Vollesen ALH, Snoer A, Beske RP, Guo S, Hoffmann J, Jensen RH, Ashina M. Effect of Infusion of Calcitonin Gene-Related Peptide on Cluster Headache Attacks: A Randomized Clinical Trial. JAMA Neurol. 2018 Oct 1;75(10):1187-1197. doi: 10.1001/jamaneurol.2018.1675.

  PMID: 29987329 BACKGROUND

• Vollesen ALH, Snoer A, Chaudhry B, Petersen AS, Hagedorn A, Hoffmann J, Jensen RH, Ashina M. The effect of pituitary adenylate cyclase-activating peptide-38 and vasoactive intestinal peptide in cluster headache. Cephalalgia. 2020 Nov;40(13):1474-1488. doi: 10.1177/0333102420940689. Epub 2020 Sep 22.

  PMID: 32962406 BACKGROUND

• Kadir RRA, Alwjwaj M, Bayraktutan U. MicroRNA: An Emerging Predictive, Diagnostic, Prognostic and Therapeutic Strategy in Ischaemic Stroke. Cell Mol Neurobiol. 2022 Jul;42(5):1301-1319. doi: 10.1007/s10571-020-01028-5. Epub 2020 Dec 24.

  PMID: 33368054 BACKGROUND

• Gallardo VJ, Gomez-Galvan JB, Asskour L, Torres-Ferrus M, Alpuente A, Caronna E, Pozo-Rosich P. A study of differential microRNA expression profile in migraine: the microMIG exploratory study. J Headache Pain. 2023 Feb 17;24(1):11. doi: 10.1186/s10194-023-01542-z.

  PMID: 36797674 BACKGROUND

MeSH Terms

Conditions

Cluster Headache; Headache; Migraine Disorders

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Roberto De Icco, MD, PhD

CONTACT

00390382380387; roberto.deicco@mondino.it

Francescantonio Cammarota, MD

CONTACT

00390382380387; francesco.cammarota@mondino.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 16, 2024
• Study Start: March 1, 2023
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: July 16, 2024

Record last verified: 2024-07

Locations

IT (1)