Suppressive Functions of Regulatory T Cells in Migraine (SIIM-reg)

June 18, 2026 updated by: University Hospital, Clermont-Ferrand

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Migraine is a major and global public health concern that affects 14% of the population worldwide. It is 2 to 3 times more prevalent in women than men and is the second leading cause of disability. Many patients remain unresponsive to currently available treatments. As evidenced in different studies, including our own, several auto-immune and inflammatory disorders, such as multiple sclerosis, are associated with a higher prevalence of migraine and a higher risk for migraine chronification (at least 15 headache days per month) compared to the general population. These findings suggest that inflammation may play an important role in migraine chronification. Cytokine and immune cell dysregulations have been evidenced in the disease but the role of inflammation in migraine pathophysiology remains unclear. Among T lymphocytes, regulatory T (Treg) cells play an important role in maintaining immune homeostasis. They regulate pro-inflammatory effector T (Teff) cells and proinflammatory cytokine release (IL-6, IL-17, interferon-γ) through different suppressive mechanisms such as the hydrolysis of pro-inflammatory and nociceptive adenosine triphosphate (ATP) into anti-inflammatory and antinociceptive adenosine (ADO), by Treg surface enzymes CD39 and CD73, present on 40% and 6-10% of Treg cells, respectively. ADO then suppresses Teff cells by binding to their ADO receptor A2A. ATP is involved in the transduction of pain signals in migraine and its insufficient hydrolysis can lead to pain chronification. It has been evidenced that Tregs naturally suppress interferon (IFN)-γ production by Teff cells. Their CD39-positive (CD39+) subsets also suppress IL-17 production by Teff cells, whereas CD39-negative (CD39-) Tregs seem to increase IL-17 secretion. Recent studies have shown altered Treg proportions in migraine compared to controls and Treg subpopulation dysregulations, such as decreased CD39+Treg cell levels. This further suggests that Treg suppressive functions may be altered in migraine, but no functional assays have been led to confirm that.

In this study, the investigators aim to determine whether Treg cells play a role in migraine pathophysiology, by answering the following 3 separate questions: Question 1) Are Treg suppressive functions decreased in migraine patients? Question 2) Are CD39+Treg cells functionally deficient in migraine patients? Question 3) Is the hydrolytic activity of enzyme CD39 reduced in migraine patients?

Through Treg/Teff coculture the investigators will assess the ability of total Treg and CD39+Treg cells to inhibit Teff proliferation and pro-inflammatory cytokine secretion and measure the hydrolytic activity of Treg enzyme CD39 on ATP in chronic migraine patients versus healthy controls. The use of human immune cells (Treg and Teff lymphocytes) in our experiments will allow the investigators to better understand migraine pathophysiology, with a direct application to human subjects, as well as to avoid animal testing and suffering. Through its animal-free setting, following the 'Reduce, Refine, Replace (3Rs)' principle, the investigators wish to promote animal-free research and the reduction of animal use for reagent production by using recombinant antibodies for flow cytometry and synthetic medium supplements for cell culture. This study will lead to a better understanding of the role of inflammation and Treg cells in migraine pathophysiology and will provide new perspectives for the development of personalized treatments according to the immune pain profile of migraine patients.

The investigators aim to show that Treg suppressive functions are altered in migraine and that the ADO pathway is deficient. Through Treg/Teff coculture the investigators will measure the ability of Tregs to inhibit Teff proliferation and cytokine secretion and assess the CD39-related hydrolytic activity of Tregs. This will allow the investigators to study Treg cells suppressive functions on Teff cells in female patients with chronic migraine and healthy female control participants.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Females
  • 18 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Chronic migraine
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
The blood sample will drawn after a fasting period of at least 8 hours, and the questionnaire will be auto-administered
Experimental: Controls
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
The blood sample will drawn after a fasting period of at least 8 hours, and the questionnaire will be auto-administered

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Treg cell suppressive functions
Time Frame: Day 0
To measure the suppressive effect of Treg cells on Teff cells in chronic migraine patients and healthy controls
Day 0

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
CD39+ Treg cell suppressive functions
Time Frame: Day 0
To measure the suppressive effect of CD39+Treg cells on Teff cells in chronic migraine patients and healthy controls
Day 0
CD39 activity
Time Frame: Day 0
To measure the hydrolytic activity of Treg enzyme CD39 in chronic migraine patients and healthy controls
Day 0
Cytokines
Time Frame: Day 0
To measure the levels of cytokine levels in blood : interleukin (IL)-6, IL-10, IL-17, IFN-g and transforming growth factor b
Day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Clermont-Ferrand

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Xavier MOISSET, University Hospital, Clermont-Ferrand

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 4, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 4, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 16, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RBHP 2025 MOISSET

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Migraine

Clinical Trials on Blood sampling, questionnaire and phone call

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings