Tryptophan as a Modulating Factor in the Antimigraine Efficacy of Triptans (TRP-Triptans)

Migraine is a leading cause of disability, and while triptans are commonly used to treat migraine attacks, over 20% of patients don't respond well to them. This study aims to understand why some people don't benefit from triptans. One key focus is tryptophan, an amino acid that plays a role in migraine and is involved in producing serotonin, which affects pain and inflammation. The study will compare levels of tryptophan and its by-products in patients who respond well to triptans versus those who don't. It will also look at how conditions like inflammatory bowel disease may affect tryptophan absorption. The goal is to improve migraine treatments tailored to different patient needs, though participants may not experience immediate personal benefits.

Study Overview

• Status: Recruiting
• Conditions: Migraine
• Intervention / Treatment: Biological: Blood collection

Detailed Description

Migraine is a leading cause of disability worldwide. Triptans are medications used to treat migraine attacks. They work mainly in two ways: by narrowing the blood vessels in the brain and by stopping the release of substances that cause pain and inflammation. Triptans help relieve migraine pain and other symptoms, like digestive problems, light sensitivity, and disability during an attack. However, more than 20% of patients do not respond well to these medications, and the reasons for this are not well understood.

Tryptophan is an essential amino acid, which means it must come from food because the body cannot produce it. Tryptophan plays an important role in migraines, especially through its by-products, such as serotonin and kynurenine. Research has shown that problems with tryptophan metabolism can make migraines worse, along with other sensory symptoms.

Although no study has directly linked tryptophan to the effectiveness of triptans, the investigators found in a preclinical study that a low-tryptophan diet could reduce the effectiveness of sumatriptan, one of the most commonly used triptans. A deficiency in tryptophan can occur when the body has trouble absorbing it from the intestines. Conditions like inflammatory bowel diseases (such as irritable bowel syndrome or Crohn's disease) or diabetes can affect this absorption, which might reduce the body's ability to process tryptophan.

This study aims to better understand how tryptophan might affect resistance to triptans in migraine patients. The investigators will compare blood levels of tryptophan and its by-products in patients who respond well to triptans versus those who do not. If participants are having a lumbar puncture as part of their regular check-up, the investigators will also examine these substances in the cerebrospinal fluid. Additionally, the investigators will explore any connection between tryptophan metabolism and inflammatory bowel disease.

• Study Type: Observational
• Enrollment (Estimated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lise Laclautre; Phone Number: 0033473754027; Email: promo_interne_drci@chu-clermontferrand.fr

Study Locations

• France
  • Clermont-Ferrand, France
    • Recruiting
    • CHU de Clermont-Ferrand
    • Principal Investigator: Xavier MOISSET
    • Contact: Lise Laclautre; Email: promo_interne_drci@chu-clermontferrand.fr
    • Principal Investigator: Cristina Alba-Delgado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Participants in the study will be recruited from the following centers:

• Centre 01: CHU de Clermont-Ferrand, Gabriel Montpied site, located at 58 Rue Montalembert, 63000 Clermont-Ferrand, France.
• Centre 02: Headache Emergency Center, Hôpital Lariboisière, located at 2 Rue Ambroise Paré, 75010 Paris, France.

Description

Inclusion Criteria:

• Cisgender women, premenopausal, aged 18 to 50 years.
• Cisgender men, aged 18 to 50 years.
• Diagnosed with migraine (according to ICHD-3 criteria).
• Diagnosed as responders or non-responders to triptans (according to the criteria of Sacco et al., 2022).
• Permitted comparison groups include: triptans used alone or in combination with other migraine treatments (e.g., NSAIDs, acetaminophen, ergotamine, opioids, antiemetics).
• All routes of administration and all dosages.
• Affiliation with a social security system.

Exclusion Criteria:

• Patients under guardianship, curatorship, deprivation of liberty, or legal protection
• Pregnant and breastfeeding women

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Migraineurs responding to triptans; Blood collection	Biological: Blood collection; Blood sampling. For patients who have had their cerebrospinal fluid sample taken as part of their treatment, a surplus sample will be used to perform the same measurements.
Migraine sufferers resistant to triptans; Blood collection	Biological: Blood collection; Blood sampling. For patients who have had their cerebrospinal fluid sample taken as part of their treatment, a surplus sample will be used to perform the same measurements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma tryptophan levels	Variation in plasma tryptophan levels between triptan-resistant and triptan-responsive migraine patients.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serotonin levels	Variation in plasma serotonin levels between triptan-resistant and triptan-responsive migraine patients.	Baseline
Kynurenine levels	Variation in plasma kynurenine levels between triptan-resistant and triptan-responsive migraine patients.	Baseline
Levels of neutral amino acids	Variation in plasma levels of neutral amino acids between triptan-resistant and triptan-responsive migraine patients.	Baseline
Levels of cytokines (IL-6, IL-10, IL-1α, IL-1β)	Variation in plasma levels of cytokines (IL-6, IL-10, IL-1α, IL-1β) between triptan-resistant and triptan-responsive migraine patients.	Baseline
Dietary tryptophan intake	Dietary tryptophan intake via a self-questionnaire on eating habits	Baseline
Inflammatory bowel disorders	Presence/absence of inflammatory bowel disorders	Baseline
Blood nutritional biomarkers	Variation in blood nutritional biomarkers (glycemia, cholesterol)	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Anxiety and Depression Scale	Tool for assessing levels of anxiety and depression in patients	Baseline
Headache Impact	The HIT-6 will be used to assess the impact of headaches on a person's daily life	Baseline

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: University of the Basque Country (UPV/EHU); Lariboisière Hospital
• Investigators: Principal Investigator: Xavier Moisset, CHU de Clermont-Ferrand; Principal Investigator: Cristina Alba-Delgado, Université d'Auvergne

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: September 10, 2025
• First Submitted That Met QC Criteria: September 10, 2025
• First Posted (Actual): September 17, 2025

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: inflammatory diseases; Triptan; Tryptophan
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: RBHP 2025 MOISSET 4; 2025-A01152-47 (Other Identifier: 2025-A01152-47)

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