Clinical Research Directory

Migraine and Endometriosis: The FEMININE Study

Migraine and endometriosis are common conditions that mainly affect females of reproductive age. Both can cause significant pain and have a strong impact on the quality of life. Increasing evidence suggests that these two conditions often occur together, and that females who have both may experience more severe symptoms than those with only one of them. However, the reasons why migraine and endometriosis are linked are still not well understood. Some biological factors may help explain this connection. One of them is a molecule called calcitonin gene-related peptide (CGRP), which plays an important role in migraine and may also be involved in pain and inflammation in endometriosis. In addition, hormonal changes during the menstrual cycle, especially fluctuations in estrogen levels, may influence symptoms in both conditions. Genetic and epigenetic factors may also contribute to this association. The main hypothesis of this study is that females who have both migraine and endometriosis have a distinct clinical and biological profile compared to females who have only migraine or only endometriosis. In particular, it is expected that differences will be observed in CGRP levels and hormonal patterns across the menstrual cycle. The FEMININE study is a prospective observational study that will follow females over several menstrual cycles. It will include three groups: females with both migraine and endometriosis, females with migraine only, and females with endometriosis only. Participants will record their symptoms in diaries and will provide blood samples at specific times of the menstrual cycle. The main goal of the study is to compare CGRP levels between groups. Additional goals include describing differences in symptoms, menstrual-related migraine, hormonal levels, and selected genetic and epigenetic markers. By improving the understanding of how migraine and endometriosis are related, this study aims to support better diagnosis and more personalized care for females affected by these conditions.

Headache Education and Awareness vs. Daily Mindfulness Strategies - Understanding Pain

The goal of this study (supported by and included in the NIH HEAL Initiative: https://heal.nih.gov/) is to learn if a fully virtual study comparing two telehealth group interventions for adolescents with migraine is feasible and acceptable: 1. Telehealth group mindfulness-based intervention 2. Telehealth group headache education

Pericranial and General Sensitivity in Patients With Primary Headache

Primary headaches such as migraine and tension type headache are among the most common neurological disorders and frequently cause significant disability and reduced quality of life. Increasing evidence suggests that these headaches may share biological mechanisms with temporomandibular disorders, a group of conditions affecting the jaw muscles and temporomandibular joint. Both conditions are also often associated with other chronic pain disorders, suggesting that altered pain processing and sensitization of the nervous system may play an important role in their development. Despite these observations, few studies have simultaneously evaluated local muscle tenderness around the head and neck, generalized pain sensitivity in other parts of the body, and the presence of additional chronic pain conditions in patients with primary headaches. Understanding how these factors interact may help clarify why some patients develop more severe or persistent headache disorders and may improve future diagnostic and treatment strategies. The aim of this multicenter observational study is to compare patients with primary headaches to healthy individuals without headaches. The study will assess sensitivity of muscles around the head and neck, general pain sensitivity at distant body sites, the presence of temporomandibular disorders, and the number of other chronic pain conditions. Participants will also complete questionnaires about pain symptoms and related health conditions. Participants will undergo a clinical examination performed by trained clinicians, including manual assessment of tenderness in head and neck muscles and measurement of pressure pain thresholds using a handheld device. Additional evaluations will include standardized questionnaires about pain intensity, pain distribution, and symptoms related to central sensitization. Cervical motor and sensorimotor function will also be evaluated using a wearable sensor system. By comparing individuals with primary headaches and healthy controls, the study aims to better understand the relationship between headache disorders, jaw related pain conditions, and general pain sensitivity. The results may contribute to improved clinical assessment and a more comprehensive understanding of the mechanisms underlying headache and related pain disorders.

Study of Oral Atogepant Tablets to Assess Safety and Efficacy in Adult Participants With Migraine

A migraine attack is a moderate or severe headache that usually occurs on one side of the head and is often accompanied by throbbing, sensitivity to light, sensitivity to sound, nausea, or other symptoms. The main goal of the study is to see if atogepant is effective, safe, and well-tolerated in treating migraine attacks quickly. Atogepant is a medicine currently approved for the preventive treatment of migraine in adults and has been shown to be effective and well tolerated when taken daily to prevent migraine attacks. This study includes double-blind phase means that neither the participants nor the study doctors know who is given which study treatment (atogepant or placebo) followed by an open-label phase meaning that both participants and study doctors know which study treatment is given. All participants will receive atogepant during the open-label part of the study. This study will include 1300 participants aged 18-75 years with a history of migraine at approximately 160 sites across the world. All participants will receive both atogepant and placebo to treat qualifying migraines. At the start of the study, participants will be randomized to 1 of 4 dosing sequences to determine when they will receive atogepant and when they will receive placebo during the study. After treating 4 qualifying migraine attacks, participants will receive open-label atogepant for any additional migraine attacks they have until the end of the study (Week 24). There may be a bigger responsibility for participants in this study than there would be in participants receiving standard of care treatment. participants will attend regular visits during the study at a hospital or clinic, as well as telephone visits, and the effects of treatment will be checked by completion of questionnaires in an electronic diary, medical assessments, blood tests, and checking for side effects.

Comparative Effectiveness of Migraine Preventive Medications: The APT Comparison Study

This goal of this study is to compare three medications used for migraine preventive treatment. This study will compare atogepant, a newer migraine preventive medication, with two older preventive medications, topiramate and propranolol. It will be determined if one works better and is more tolerable than the others. Research participants will: * Be randomly assigned to one of the three medications. * Provide information about their migraine pattern using a daily headache diary and during research visits.

Study to Assess Function and Satisfaction of Oral Ubrogepant in Adult Participants After Multiple Migraine Attacks In Canada

Migraine is a neurological disease characterized by moderate or severe headache, associated with nausea, vomiting, and/or sensitivity to light and sound. This study will evaluate function and satisfaction with oral ubrogepant in treating adult participants after multiple migraine attacks. Ubrogepant is a drug approved for the acute treatment of migraine in adults. Approximately 167 participants will be enrolled in approximately 10-15 sites across Canada. Participants will receive ubrogepant as prescribed by their physician according to their routine clinical practice and local label. Participants will be followed for up to 12 weeks. There is expected to be no additional burden for participants in this trial. Participants will attend regular visits during the study at a hospital or clinic according to their routine clinical practice.

Migraine Manager (R01)

The objective of this trial is to test whether an online tailored intervention, Migraine Manager, is efficacious in improving headache outcomes compared to an attention control intervention in adolescents with migraines. We will conduct a randomized clinical trial to compare a sample of 80 youth (ages 11 to 17) with migraine receiving the online tailored adherence intervention to 80 youth in an attention control group. We will test whether adherence to healthy habit (hydration, regular meals, exercise, sleep) recommendations serves as a mechanism for improved headache outcomes. Clinically meaningful outcomes will be assessed by reliable, valid, and sensitive measures. The primary outcome (i.e., number of headache days) will be assessed via online daily diary pre- and post-intervention, with additional follow-up at 3, 6, 9, and 12 months. Secondary outcomes include health-related quality of life and migraine disability.

Evaluation of Pain Thresholds in Migraine Patients After Inhalation of Essential Oils: a Randomized Clinical Trial

This study will test whether inhaling essential oils can change how sensitive people with migraine are to pressure pain. Participants will be allocated to inhale lavender, peppermint, a combination of both, or a control solution (distilled water with coconut oil). Each group will have 50 participants. The inhalation will last 15 minutes and will happen only once. Before and after the inhalation, we will measure how much pressure on certain areas of the head.

Migraine Prevention With the Remote Electrical Neuromodulation (REN) Wearable: A Real-world Evidence Study

Preventive pharmacologic therapies for migraine aim to reduce attack frequency and duration and improve quality of life; however, their use, overall benefit and adherence are often limited, especially among patients with chronic migraine. Remote electrical neuromodulation (REN) is a non-invasive FDA-cleared wearable device for acute and/or preventive migraine treatment. This study evaluated the real-world efficacy and patient-reported outcomes of preventive REN use over 3 months in chronic migraine population.

Headache Prevalence and Phenotype in Myelin Oligodendrocyte Glycoprotein Antibody -Associated Disease (MOGAD)

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) is an inflammatory demyelinating disorder of the central nervous system characterized by antibodies targeting myelin oligodendrocyte glycoprotein (MOG). Although the disease most commonly presents with optic neuritis, myelitis, or acute disseminated encephalomyelitis, headache has increasingly been reported as a potentially relevant and disabling symptom. However, the prevalence and clinical characteristics of headache in MOGAD remain poorly defined. The purpose of this monocentric ambispective observational study is to evaluate the prevalence and clinical phenotype of headache in adult patients with MOGAD. The study aims to answer the following research questions: How common is headache in patients with MOGAD, what are its clinical characteristics, and does it show any correlation with any specific disease features? The primary objective is to estimate the prevalence of acute and/or chronic headache in patients with MOGAD. Secondary objectives include describing headache characteristics (location, duration, intensity, associated symptoms, and response to treatment), assessing the presence and evolution of pre-existing primary headache disorders, and exploring potential associations between headache and laboratory or neuroradiological findings, including anti-MOG antibody titers, cerebrospinal fluid (CSF) oligoclonal bands, and the location of inflammatory or demyelinating lesions on MRI. Approximately 25 adult patients with MOGAD followed at the Multiple Sclerosis Center and Headache Clinic of the Fondazione Policlinico A. Gemelli IRCCS will be included. Clinical, laboratory, and neuroradiological data will be collected retrospectively and prospectively from medical records.

Efficacy and Safety Study of Rimegepant for the Preventative Treatment of Migraine in Pediatric Subjects

The purpose of this study is to compare the efficacy and safety of rimegepant to placebo as a preventative treatment for migraine in children and adolescents ≥ 6 to \<18 years with episodic migraine.

Mind Body Balance for Pediatric Migraine

This study uses a factorial research design to evaluate a nurse delivered mind body intervention using different doses of 3 treatment components to determine the optimized treatment for headache day reduction.

Evaluation of MIG-SPRAY Treatment on Migraine

The goal of this clinical trial is to evaluate the real-world tolerability of the MIG-SPRAY device in adults aged 18-55 diagnosed with migraine (according to nternational Classification of Headache Disorders 3rd edition, code 1.1(ICHD-3)) for over 1 year. The main questions it aims to answer are: * Does MIG-SPRAY significantly reduce the composite score of expected adverse events (e.g., allergic reactions, nausea, headache) compared to no intervention, graded via a Likert scale (using the Common Terminology Criteria for Adverse Event (CTCAE v5.0))? * Are there differences in unexpected adverse events, monthly migraine frequency, or Migraine Disability Assessment (MIDAS) scores between groups? Researchers will compare the intervention group (MIG-SPRAY) to the control group (no device) to assess: 1. Tolerability (primary outcome). 2. Unexpected adverse events, migraine frequency, and disability (secondary outcomes). Participants will: * Be randomized (2:1) to MIG-SPRAY (n=30) or control (n=15). * Use an electronic diary daily to report adverse events and migraine episodes. * Complete the MIDAS questionnaire at baseline and post-treatment. * Undergo monthly physician calls to review and grade adverse events. Study design: * Post-marketing, monocentric, open-label, randomized trial (Clermont-Ferrand University Hospital). * Category 4.2 clinical investigation (CE-marked Class I device, used per labeling). * No changes to background migraine therapy permitted. Key eligibility: * Age 18-55, migraine diagnosis ≥1 year (ICHD-3). * Effective contraception (females of childbearing potential). * Social security coverage and written informed consent.

MMA Embolization for Refractory Chronic Migraine

This is a prospective, multi-center, feasibility study to investigate safety and effectiveness of TRUFILL n-BCA liquid embolic system in bilateral middle meningeal artery (MMA) embolization for the treatment of refractory chronic migraine.

NIMH Rhythms and Blues Study: A Prospective Natural History Study of Motor Activity, Mood States, and Bipolar Disorder

Background: Mood disorders, such as bipolar disorder, can have serious effects on a person s life. People with bipolar disorder are more likely to have heart disease and abuse substances. In this natural history study, researchers would like to learn more about the connection between exercise and mental health in people with and without mood disorders. Objective: To better understand relationships among physical activity, sleep, and mental health. Eligibility: People aged 8 to 60 years with a history of a mood disorder. Healthy spouses and relatives with no mood disorders are also needed. Design: Participants will be in the study up to 2 years. For up to 20 days in a row, at 4 times during the study, participants will: Complete an electronic diary on their smartphone. Participants will answer questions about their mood, health, sleep, and daily activities. Wear an activity monitor, like a wristwatch, that records how much they move. Wear a light sensor, as a necklace, to record the amount of light in their environment. Some participants will do additional tests. Twice during the study, for 3 days in a row, they will: Wear monitors to record their temperature, heart rate, and sleep. Provide saliva samples. Complete cognitive tasks on their smartphone. Participants will visit the NIH clinic 2 times. They will have a physical exam, with blood and urine tests. They will wear a heart monitor. They will ride a stationary bike for 30 minutes. They may have an imaging scan. Some participants will stay overnight. They will go to sleep wearing a cap to measure their brain activity.

AI-assisted Migraine Education: Efficacy, Safety and Patients' Acceptance

Migraine affects 1 in 7 people globally, significantly impacting quality of life and economic productivity. Despite its prevalence, limited awareness leads to misdiagnosis, inadequate treatment, and stigmatization. AI can enhance migraine management through improved diagnosis, prediction, and personalized education. The primary objective of this study is to determine if adding AI-assisted migraine education to standard education improves patients' understanding of their condition more effectively.

A Study With Eptinezumab in Children and Adolescents (6 to 17 Years) With Chronic or Episodic Migraine

The main goal of the study is to assess the long-term safety of eptinezumab on children and adolescents ages 6 to 17 with chronic or episodic migraine.

Effect of Transcutaneous Auricular Trigeminal Nerve Stimulation on Migraine

This randomized, sham-controlled, and double-blind clinical study aims to investigate the effects of transcutaneous auricular trigeminal nerve stimulation (taTNS) on intensity of headache, sleep quality, level of disability, and Heart rate variability (HRV) in patients with migraine. The inclusion criteria were: (1) being aged 18-45 years, (2) being literate in Turkish, (3) having been diagnosed with episodic migraine with aura and migraine without aura by a neurologist according to the International Classification of Headache Disorders, (4) having a history of migraine for at least 6 months with at least 2 attacks per month in the last 3 months. The exclusion criteria were: (1) being pregnant or breastfeeding; (2) regular use of analgesics or non-steroidal anti-inflammatory drugs for more than 15 days per month; (3) pacemaker implantation; (4) a history of addiction, syncope or abnormal ECG findings; (5) a history of intracranial haemorrhage or significant head trauma; (6) a diagnosis of epilepsy, severe anxiety or depression; (7) other types of headaches, including paresthesia or medication-overuse headaches; and (8) cognitive, visual, or auditory problems that would prevent participation in the study. The TaTNS was applied to the intervention and control (sham) groups by a physiotherapist (AP). The treatment session lasted 20 minutes and will apply three days a week for 12 weeks. The physical (age, gender, height, body weight), sociodemographic (marital status, education level), and clinical characteristics (chronic diseases, medications used, age of migraine onset, migraine frequency in the last month, migraine treatment history) of participants will be recorded. Primary outcome measurement: Migraine headache intensity (VAS), disability level (Migraine Disability Assessment Scale \[MIDAS\]), sleep quality (Pittsburgh Sleep Quality Index \[PSQI\]), Secondary outcome measurement: Heart rate variability (HRV) (Polar H7 device) will be assessed. All calculations will be performed using 5-minute Polar H7 recordings cleaned of artifacts, using Kubios HRV Premium software (Kubios Oy, Finland) in accordance with international standards.

A Dose-finding Trial With Lu-AG09222 in Adults With Migraine Who Have Not Been Helped by Prior Preventive Treatments

The purpose of this trial is to determine which doses of Lu AG09222 are recommended to help prevent migraines. People who join this trial have already tried 1 to 4 other available medications to prevent their migraines, but these medications have not helped them.

Bilateral Embolization of the Middle Meningeal Arteries for Refractory Chronic Migraine

This study is to test the safety and feasibility of a procedure called embolization of the middle meningeal arteries (MMA), using a product called Onyx. Embolization creates a plug in the arteries. MMA embolization with Onyx is not approved for use in patients with migraines, but is currently used in patients with subdural hematomas. The FDA is allowing the use of Onyx in this study. It is thought that by using Onyx to block the middle meningeal arteries, the amount of migraine-causing substances which are released into the brain's bloodstream will be reduced. The company that manufactures Onyx, Medtronic, is providing the supplies for this study. Participants will be in the study for about 8 months after enrolling, including 6 months of follow up after the procedure. The participants will be asked to complete a daily headache diary and continue the participant's regular migraine medications. Participants will also have several clinic visits and be asked to provide blood samples for research.

Selective Activation of the Adrenomedullin Receptors in Migraine

Adrenomedullin is a neuropeptide implicated in the pathogenesis of migraine. This study investigates whether its administration, after pre-treatment with erenumab (a CGRP-receptor blocking monoclonal antibody), can trigger migraine attacks in individuals with migraine without aura.

Tryptophan as a Modulating Factor in the Antimigraine Efficacy of 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.

A Trial of Eptinezumab in Participants With Migraine and Insufficient Response to Anti-CGRP Medications

The main goal of this trial is to learn whether eptinezumab improves migraine symptoms and quality of life of participants with migraine who did not perceive a sufficient improvement during previous treatment with therapies targeting calcitonin gene-related peptide (CGRP).

Responding With Evidence and Access for Childhood Headaches

This comparative effectiveness study will clarify current first-line preventive treatment approaches for use by neurologists, psychologists, and primary care providers in the context of real world care, and will demonstrate the feasibility of Cognitive Behavioral Therapy (CBT) via telehealth for youth with migraine. The focus is on applying evidence-based care and enhancing access to it. CBT via telehealth while taking a clinically-prescribed, pill-based prevention therapy (amitriptyline) will be compared to CBT via telehealth alone.