Suppressive Functions of Regulatory T Cells in Migraine

NCT07067112 | Not Yet Recruiting

• 1 other identifier: RBHP 2025 MOISSET
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Migraine is a frequent, disabling condition, of great social and economical impact worldwide. This condition is more frequent in women and subjects with autoimmune and/or inflammatory diseases. Cytokine and immune cell dysregulations have been evidenced in migraine. Inflammation seems to play an important role in migraine chronification; however, the inflammatory mechanisms involved in migraine pathophysiology remain unclear. Regulatory T (Treg) cells play a central role in maintaining immune homeostasis. They regulate effector T (Teff) cell proliferation and cytokine production, through several suppressive mechanisms, such as the hydrolysis of adenosine triphosphate (ATP) into adenosine (ADO), mediated by surface enzymes Cluster Differentiation 39 (CD39) and Cluster Differentiation 73 (CD73). ATP is involved in pain processes in migraine, and insufficient hydrolysis could participate in pain chronification. Recent studies suggest altered proportions of Treg cells in migraine, and decreased levels of CD39-positive (CD39+) Treg cells, suggesting Treg suppressive functions may be decreased in the disease. However, there have been no functional studies to date to confirm this hypothesis. The investigators believe Treg suppressive functions may be decreased in migraine, and that such alterations may be caused by a malfunction in the ADO pathway.

Conditions

Chronic Migraine

Keywords

Migraine; Inflammation; Immune system; Regulatory T cells

Outcome Measures

Primary Outcomes (1)

• Treg cell suppressive functions

  To measure the suppressive effect of Treg cells on Teff cells in chronic migraine patients and healthy controls

  Day 0

Secondary Outcomes (3)

• CD39+ Treg cell suppressive functions

  Day 0

• CD39 activity

  Day 0

• Cytokines

  Day 0

Study Arms (2)

Chronic migraine

EXPERIMENTAL

Chronic migraine patients will donate 100 milliliters (mL) of peripheral and venous blood, answer a questionnaire and 2 phone calls (one at day 1 and the other at day 3 from the blood test).

Biological: Blood sampling, questionnaire and phone call

Controls

EXPERIMENTAL

Non-migraine controls will donate 100 mL of peripheral and venous blood, answer a questionnaire and 2 phone calls (one at day 1 and the other at day 3 from the blood test).

Biological: Blood sampling, questionnaire and phone call

Interventions

Blood sampling, questionnaire and phone call BIOLOGICAL

The blood sample will drawn after a fasting period of at least 8 hours, and the questionnaire will be auto-administered

Chronic migraine; Controls

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Females
• to 50 years old
• Chronic migraine participants : chronic migraine (at least 15 days of headache/month, according to the International Classification of Headache Disorders, 3rd edition criteria

You may not qualify if:

• BMI \< or = 17kg/m² or \> or = 30kg/m²
• Diagnosis or suspicion of type 2 diabetes, auto-immune or inflammatory diseases, immunodeficiency diseases
• Diagnosis of headache of non-migraine origin, except for tension type headache \< or = 4 days per month (i.e.: cluster headache, post-traumatic headache, cerebral tumour…)
• Pregnancy, delivery, miscarriage, breastfeeding, participation in a medically assisted human reproduction program (ovary stimulation/hormone therapy) \< 3 months before blood sampling
• Menopause, hysterectomy, or bilateral oophorectomy
• Flare of the autoimmune/inflammatory disease of interest \< 1 month before blood sampling
• Modification of maintenance therapy for the autoimmune/inflammatory disease of interest (start, change of molecule, interruption) \< 3 months before blood sampling
• Modification of prophylactic anti-migraine therapy (start, change of molecule, interruption) \< 3 months before blood sampling (for migraine participants)
• Hormone therapy (besides contraception and treatment of endometriosis)
• Transplantation (solid organ or bone marrow)
• Cancer (active or remitting) \< 1 year before blood sampling (solid organ or blood)
• Haematologic disease (benign or malignant) of the lymphoid lineage
• Guardianship, curatorship, safeguard of justice or deprivation of liberty
• For controls : diagnosis of migraine

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (1)

CHU Clermont-Ferrand

Clermont-Ferrand, France

Location

Related Publications (19)

• Stovner LJ, Hagen K, Linde M, Steiner TJ. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. J Headache Pain. 2022 Apr 12;23(1):34. doi: 10.1186/s10194-022-01402-2.

  PMID: 35410119 BACKGROUND

• Ashina M. Migraine. N Engl J Med. 2020 Nov 5;383(19):1866-1876. doi: 10.1056/NEJMra1915327. No abstract available.

  PMID: 33211930 BACKGROUND

• Barbanti P, Aurilia C, Egeo G, Torelli P, Proietti S, Cevoli S, Bonassi S; Italian Migraine Registry study group. Late Response to Anti-CGRP Monoclonal Antibodies in Migraine: A Multicenter Prospective Observational Study. Neurology. 2023 Sep 12;101(11):482-488. doi: 10.1212/WNL.0000000000207292. Epub 2023 Apr 18.

  PMID: 37072224 BACKGROUND

• Moisset X, Giraud P, Dallel R. Migraine in multiple sclerosis and other chronic inflammatory diseases. Rev Neurol (Paris). 2021 Sep;177(7):816-820. doi: 10.1016/j.neurol.2021.07.005. Epub 2021 Jul 27.

  PMID: 34325914 BACKGROUND

• Moisset X, Ouchchane L, Guy N, Bayle DJ, Dallel R, Clavelou P. Migraine headaches and pain with neuropathic characteristics: comorbid conditions in patients with multiple sclerosis. Pain. 2013 Dec;154(12):2691-2699. doi: 10.1016/j.pain.2013.07.050. Epub 2013 Aug 2.

  PMID: 23911697 BACKGROUND

• Edvinsson L, Haanes KA, Warfvinge K. Does inflammation have a role in migraine? Nat Rev Neurol. 2019 Aug;15(8):483-490. doi: 10.1038/s41582-019-0216-y. Epub 2019 Jul 1.

  PMID: 31263254 BACKGROUND

• Thuraiaiyah J, Erritzoe-Jervild M, Al-Khazali HM, Schytz HW, Younis S. The role of cytokines in migraine: A systematic review. Cephalalgia. 2022 Dec;42(14):1565-1588. doi: 10.1177/03331024221118924. Epub 2022 Aug 12.

  PMID: 35962530 BACKGROUND

• Nurkhametova D, Kudryavtsev I, Khayrutdinova O, Serebryakova M, Altunbaev R, Malm T, Giniatullin R. Purinergic Profiling of Regulatory T-cells in Patients With Episodic Migraine. Front Cell Neurosci. 2018 Sep 25;12:326. doi: 10.3389/fncel.2018.00326. eCollection 2018.

  PMID: 30319363 BACKGROUND

• Loza MJ, Anderson AS, O'Rourke KS, Wood J, Khan IU. T-cell specific defect in expression of the NTPDase CD39 as a biomarker for lupus. Cell Immunol. 2011;271(1):110-7. doi: 10.1016/j.cellimm.2011.06.010. Epub 2011 Jul 18.

  PMID: 21763644 BACKGROUND

• Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol. 2008 Jul;8(7):523-32. doi: 10.1038/nri2343.

  PMID: 18566595 BACKGROUND

• Giniatullin R, Nistri A, Fabbretti E. Molecular mechanisms of sensitization of pain-transducing P2X3 receptors by the migraine mediators CGRP and NGF. Mol Neurobiol. 2008 Feb;37(1):83-90. doi: 10.1007/s12035-008-8020-5. Epub 2008 May 6.

  PMID: 18459072 BACKGROUND

• Fletcher JM, Lonergan R, Costelloe L, Kinsella K, Moran B, O'Farrelly C, Tubridy N, Mills KH. CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J Immunol. 2009 Dec 1;183(11):7602-10. doi: 10.4049/jimmunol.0901881. Epub 2009 Nov 16.

  PMID: 19917691 BACKGROUND

• Faraji F, Shojapour M, Farahani I, Ganji A, Mosayebi G. Reduced regulatory T lymphocytes in migraine patients. Neurol Res. 2021 Aug;43(8):677-682. doi: 10.1080/01616412.2021.1915077. Epub 2021 Apr 14.

  PMID: 33853506 BACKGROUND

• Arumugam M, Parthasarathy V. Reduction of CD4(+)CD25(+) regulatory T-cells in migraine: Is migraine an autoimmune disorder? J Neuroimmunol. 2016 Jan 15;290:54-9. doi: 10.1016/j.jneuroim.2015.11.015. Epub 2015 Nov 28.

  PMID: 26711570 BACKGROUND

• Yang L, Zhou Y, Zhang L, Wang Y, Zhang Y, Xiao Z. Aryl hydrocarbon receptors improve migraine-like pain behaviors in rats through the regulation of regulatory T cell/T-helper 17 cell-related homeostasis. Headache. 2023 Sep;63(8):1045-1060. doi: 10.1111/head.14599. Epub 2023 Aug 4.

  PMID: 37539825 BACKGROUND

• Anaya JM. Common mechanisms of autoimmune diseases (the autoimmune tautology). Autoimmun Rev. 2012 Sep;11(11):781-4. doi: 10.1016/j.autrev.2012.02.002. Epub 2012 Feb 12.

  PMID: 22353402 BACKGROUND

• Guo Z, Zhang J, Liu X, Unsinger J, Hotchkiss RS, Cao YQ. Low-dose interleukin-2 reverses chronic migraine-related sensitizations through peripheral interleukin-10 and transforming growth factor beta-1 signaling. Neurobiol Pain. 2022 Jun 13;12:100096. doi: 10.1016/j.ynpai.2022.100096. eCollection 2022 Aug-Dec.

  PMID: 35733705 BACKGROUND

• Okimura H, Tanaka Y, Fujii M, Shimura K, Maeda E, Ito F, Khan KN, Nakamura Y, Mori T, Kitawaki J. Changes in the proportion of regulatory T cell subpopulations during menstrual cycle and early pregnancy. Am J Reprod Immunol. 2022 Dec;88(6):e13636. doi: 10.1111/aji.13636. Epub 2022 Oct 21.

  PMID: 36217280 BACKGROUND

• Douge A, Vituret C, Carraro V, Parry L, Coudy-Gandilhon C, Lemal R, Combaret L, Maurin AC, Averous J, Jousse C, Bay JO, Verrelle P, Fafournoux P, Bruhat A, Rouzaire P. Temporal regulation of transgene expression controlled by amino acid availability in human T cells. HLA. 2024 Jan;103(1):e15252. doi: 10.1111/tan.15252. Epub 2023 Oct 17.

  PMID: 37848366 BACKGROUND

MeSH Terms

Conditions

Migraine Disorders; Inflammation

Interventions

Blood Specimen Collection; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Xavier MOISSET

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lise Laclautre

CONTACT

334.73.754.963; promo_interne_drci@chu-clermontferrand.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be enrolled in either the chronic migraine or control group for comparison between chronic migraine patients and controls.

Study Record Dates

• First Submitted: July 4, 2025
• First Posted: July 16, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: January 21, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)