Clinical Research Directory

App-based Breathing Program for Migraine Relief

Migraine is one of the most common neurological disorders, characterized by recurrent headaches, sensitivity to light and movement, nausea, and autonomic dysregulation. Although mind-body interventions like biofeedback have shown their efficacy, they remain underutilized due to barriers such as transportation, time constraints, lack of awareness, stigma, and cost. A targeted approach to enhancing HRV is HRV biofeedback (HRVB), a technique using visual or auditory feedback to help people regulate HRV through slow-paced breathing and positive emotional regulation to promote ANS balance and emotional resilience. Investigators will conduct a remotely delivered pilot RCT of an 8-week, 10 min/day, novel app-based HRVB intervention compared to a sham control intervention (matching intervention time and attention with no biofeedback component) in adult with chronic migraine. Investigators hypothesize data collected from the study will: a) support the feasibility and acceptability of the remotely delivered app-based HRVB intervention among adults with chronic migraine, and b) provide insights into refining the intervention by examining patterns of change in migraine and psychological outcomes from pre- to post-intervention.

Long-term Atogepant in Real-world Practice

This prospective multicentre observational study aims to evaluate the long-term effectiveness, safety, tolerability, and treatment persistence of atogepant for migraine prevention in routine clinical practice. Adult patients with migraine initiating atogepant across 15 tertiary Headache Units in Spain are followed for 12 months. Clinical outcomes, including monthly headache days, monthly migraine days, medication overuse, adverse events, treatment discontinuation, and patient-reported outcomes in a subset of participants, are assessed at baseline and after 3, 6, and 12 months. The study also characterizes different response trajectories, including sustained, delayed, and transient responses, in a real-world population with high disease burden and multiple prior preventive treatment failures.

Lidocaine Infusion Treatment for Subarachnoid Hemorrhage Headaches

The goal of this observational study is to evaluate intravenous lidocaine efficacy and safety in treating headache following non-traumatic subarachnoid hemorrhage. Through this prospective analysis, the investigators hope to: 1. show that intravenous lidocaine infusion causes a clinically significant reduction in pain scores in patients with moderate/severe headache pain following non-traumatic subarachnoid hemorrhage; 2. show that intravenous lidocaine infusion is safe in treating headache following non-traumatic subarachnoid hemorrhage; 3. and report vasospasm prevalence in the cohort. Participants will receive lidocaine infusion as treatment for non-traumatic subarachnoid hemorrhage headache and provide pain scores (on a numeric pain scale) every two hours the patients are awake for a maximum of seven days. Monitoring for vasospasm will occur as part of the patients regular medical care.

BLOCK-SAH - PPF-Block for Post-SAH Headache

BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial with a sequential parallel comparison design (SPCD) of bilateral pterygopalatine fossa (PPF) injections with 20mg ropivacaine + 4mg dexamethasone (active, PPF-block) compared to saline (placebo) for headache in survivors of aneurysmal subarachnoid hemorrhage (SAH), while monitoring intracranial arterial mean flow velocities with transcranial Doppler (TCD) peri-intervention (intervention = PPF-injections: active or placebo)

Muscle Position and Dry Needling Efficacy

Currently, no previous studies have investigated how the position of a muscle before dry needling may influence the outcome and effectiveness of the treatment. This study aims to demonstrate whether the position of the upper trapezius muscle during dry needling treatment influences the outcome of that treatment in subjects with neck pain. A total of 46 participants with chronic neck pain will be recruited and randomly assigned to two groups: a dry needling group with the muscle in a stretched position and a dry needling group with the muscle in a shortened position. A total of two treatment sessions will be performed, separated by a 7-day interval. The primary outcome measure will be the intensity of neck and head pain, measured using the visual analog scale (VAS). Other variables to be measured include the cervical disability index, kinesiophobia, and catastrophizing (using a self-completion questionnaire), as well as participants' expectations and post-needling pain.

Placebo Impacts Sleep and Pain Modulation in Chronic Pain

The goal of this free-choice parallel design clinical trial is to examine the potential beneficial effects of using open-label placebo (OLP) in improving chronic pain related outcomes and sleep quality in people with temporomandibular disorders. This study will enroll a cohort of participants with temporomandibular disorders (TMD) which lasts for more than 3 months. The main questions it aims to answer are: 1. Will participants with TMD be more likely to take open-label placebo pills if they are introduced to the effects of placebo (e.g., going through an expectation management session)? 2. Will taking open-label placebo plus expectation management improve chronic pain related outcomes, such as chronic pain intensity, interference, levels of anxiety and depression, in the cohort of TMD? 3. Will open-label placebo plus expectation management improve sleep quality in participants suffering from TMD? To answer the above questions, participants with TMD will be randomly assigned to three groups: 1. Open-label placebo plus expectation management group, where participants will complete a 1-hour discussion session about their expectations toward open-lable placebo intervention, and then take 1 open-labe placebo pill per day for a total of 45 days. 2. Open-label placebo only group where participants will be asked to take open-label placebo pills, one pill per day, for a total of 45 days. 3. standard of care group where participants will maintain their usual care without introducing open-label placebo to them during the 45 days monitoring. Researchers will compare the chronic pain intensity, interference, mood, anxiety, and sleep quality between the open-label placebo group and the wait-list group. Daily chronic pain will be measured using visual analog scale (VAS) ranging from 0=no pain at all to 100=maximum tolerable pain. Chronic pain interference using Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference and pain behavior. Anxiety and depression will be measured using PROMIS-anxiety, and PROMIS-depression scales respectively. Finally, sleep quality will be quantified using the objective measurement Motion Watch during the 45 days intervention and monitoring. In order to have a rigorous measurement of the baseline pain and sleep fluctuation, this study will include a 7-day phenotyping period before the starting of the 45-day intervention and monitoring. During the 7-day phenotyping period, participants will record their daily chronic pain and sleep quality using polysomnography.

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.

Utilization of 60-Day Peripheral Nerve Stimulation of the Occipital Nerves for the Treatment of Headache

This prospective observational cohort study will evaluate clinical outcomes and health care resource utilization among adults who, independent of research participation, are clinically scheduled to undergo temporary 60-day occipital nerve peripheral nerve stimulation (PNS) as part of routine care for refractory headache disorders.

Sequential, Multiple Assignment, Double Randomized Preference, Migraine Behavioral Trial

This study will unpack the behavioral intervention for migraine and determine the optimum combinations. In addition, the study will test preference and self-selection effects during the trial.

Determining the Utility of a Behavioral Intervention in Chronic Migraine

This proposal will involve a pilot study to evaluate the feasibility, acceptability, and outcomes of a lifestyle behavior protocol in managing chronic migraine. Additionally, the proposal will investigate biomolecules that are uniquely involved in chronic migraine patients who respond to the protocol. Successful completion of this proposal will inform the design of a future full-scale behavioral clinical trial to control chronic migraine.

SubArachnoid Hemorrhage HEadache Treated by Lumbar Puncture

Headache control is one of the major challenges in patients who suffered an acute aneurysmal subarachnoid hemorrhage (aSAH). Headache affects 90% of the patient and is resistant to the major pain medication. It results from the increased intracranial pressure and the inflammation caused by the accumulation of arterial blood in the subarachnoid space. Hemorrhagic cerebrospinal fluid (CSF) removal by a lumbar puncture (LP), is well tolerated, reduces intracranial pressure and accelerates the clearance of the blood products from CSF. Nonetheless it has never been tested in a randomized trial. The investigators aim to compare in patients who experienced a low grade aSAH, the variation of headache intensity after CSF removal by LP vs. Sham LP in addition to predefined analgesic protocol management.

Intranasal Sphenopalatine Ganglion Blockade for Headaches Following Aneurysmal Subarachnoid Hemorrhage

In patients with bleeding from a brain aneurysm, severe headache is the most common complaint. However, the pain is difficult to treat. The use of standard pain medications is common, but pain control remains poor. Additionally, pain medicines have multiple side effects including sedation, interference with breathing, intestinal cramping, low blood pressure, and the risk of addiction. In the present study, the investigators will examine the use of a medication to block the sphenopalatine ganglion which is a bundle of nerves that includes nerves that cause head pain. This block is performed by spraying numbing medication into the back of the nasal cavity on both sides. This particular pain medication does not have the side effects discussed above. The purpose of the study is to see if this treatment will decrease pain without causing unwanted side effects. All patients in the study will receive standard pain medicine as needed for headache. Information will be collected from the patient's medical chart on the amount of pain medication used and the amount of pain the patient describes having. The average pain will be calculated for the first 24 hours the patient is in the hospital. At that point, the patient will receive pain medication sprayed into the back of the nasal cavity on both sides. Patients will also receive this treatment 3 days later. Following these treatments, information will be obtained on the average amount of pain, and how much other pain medication is used. The investigators will look at the amount of pain and the amount of other pain medicine used over the first 24 hours before the nasal pain medicine treatment and compare it to the time after the treatments to see if the amount of pain decreases and if the amount of other pain medicine needed decreases as well. Six months after discharge, the patient will be contacted by phone to find out more information about how much head pain they had after discharge from the hospital.

Sphenopalatine Ganglion Block for Post-Dural Puncture Headache

This pilot randomised controlled trial compared sphenopalatine ganglion block (SPGB) using intranasal 2% lidocaine versus conservative management (bed rest and aggressive hydration) in patients who developed post-dural puncture headache (PDPH) following accidental dural puncture with 17G Tuohy needles during epidural procedures. The primary outcomes were feasibility metrics (recruitment, retention, and protocol adherence). Secondary outcomes included pain intensity measured by the Numerical Rating Scale (NRS 0-10) at 30 minutes, 12 hours, and 24 hours post-intervention; rescue analgesia requirements; mobilisation time; and adverse events.

The Effect of Osteopathic Treatment on Craniocervico-Mandibular Dysfunction

The goal of this clinical trial is to measure the effects of osteopathic manipulative treatment (OMT) on tissues of the craniocervico-mandibular unit (CCMU) in individuals with neck pain and headaches. The main questions to answer are: 1. How does OMT affect CCMU muscle stiffness 2. How does OMT affect jaw motion 3. How does OMT affect autonomic function 4. Is pain pressure threshold affected by OMT of the CCMU Participants will undergo the following interventions: 1. Photos taken to measure head and neck angles 2. Ultrasound 3. Smooth Pursuit Neck Torsion Test 4. Motion Capture 5. Autonomic Protocol 6. Algometry 7. Surveys

The Effectiveness of Acupuncture on Headaches in Women Undergoing IVF Egg Stimulation

To test the effect of acupuncture in treating headaches, as well as co-measures of stress and emotional distress, in participants during the hormonal stimulation phase prior to an oocyte retrieval. Subjects were identified females at birth experiencing a headache while undergoing a hormone stimulation cycle as part of in vitro fertilization or oocyte cryopreservation. Intervention was an individualized acupuncture treatment with needle retention for thirty minutes. Main outcome measured were headache intensity, level of stress, level of emotional distress.

LLM-Generated Lay Summaries for Brain MRI Reports

The goal of this clinical trial is to learn if a summary written by artificial intelligence (AI) helps adults understand brain MRI reports for headaches. The main question it aims to answer is: "Does adding a simple summary help readers correctly understand if a cause for the headache was found in the report?" Researchers will compare standard MRI reports to reports that include an AI-generated explanation to see if the extra summary improves understanding. Participants will: Read 6 fictional brain MRI reports online. Answer questions to check if they understood the results. Rate their satisfaction and if they feel they would need to ask a doctor for help.

Percutaneous Needle Electrolysis (PNE) on the Concha of the Ear

Headache is a very frequent symptom among the world population, the adult population with an active headache disorder are 46% for headache in general, 11% for migraine, 42% for tension-type headache and 3% for chronic daily headache. There are different therapeutic approaches for the improvement of headache. Transcutaneous stimulation of the auricular vagal nerve is being used for the treatment of headache due to the involvement of the vagus nerve in inflammation and pain modulation. On the other hand, galvanic current has shown a measurable effect by increasing parasympathetic activity. The objective of this clinical trial is to stimulate the auricular vagal nerve with galvanic current using a needle as an electrode that will be inserted into the concha of the ear. As a tool for measuring results, infrared thermography will be used to observe changes in facial skin temperature, since patients with high sympathetic activity present a characteristic pattern of "cold nose" and/or "cold patch". In addition, variables that record changes in autonomic activity such as skin conductance and heart rate variability will be collected.

Aerobic Exercise and Its Impact on Sensory, Musculoskeletal, and Psychosocial Aspects in Migraine

Migraine is a neurological disorder associated with high levels of disability and changes in sensory processing, musculoskeletal function, and psychosocial factors. Aerobic exercise is a low-cost, non-pharmacological strategy that has shown potential benefits for migraine management, but its effects on sensory perception and musculoskeletal function are not yet fully understood. This randomized controlled trial will investigate the effects of a supervised aerobic exercise program combined with pain neuroscience education compared with an active control condition in women aged 18 to 48 years diagnosed with migraine. Participants will be randomly allocated to either an intervention group, which will perform supervised aerobic exercise three times per week for 16 weeks and receive one session of pain neuroscience education, or a control group, which will receive recommendations for unsupervised physical activity at home. Outcomes related to migraine-related disability, self-reported symptoms, sensory sensitivity, and musculoskeletal function will be assessed at baseline and after the intervention period. Questionnaires will also be collected at a 6-month follow-up. The results of this study may contribute to the development of accessible and low-risk non-pharmacological treatment strategies for people with migraine.

Vagal Nerve Stimulation for Post COVID Fatigue

The purpose of this study is to evaluate the impact of vagal nerve stimulation on patients with post COVID syndrome who have fatigue and headache.

External Trigeminal Nerve Stimulation for Migraine Treatment in Pregnancy

This online registry aims to understand the potential benefits and safety of external trigeminal nerve stimulation for the treatment of migraine in pregnant women. Women do not need to use external trigeminal nerve stimulation or any other form of migraine treatment to participate in the registry. The main question it aims to answer is: Is external trigeminal nerve stimulation a safe and effective option for migraine treatment during and after pregnancy? There are no required changes in migraine treatment to participate in this registry. Participants may or may not use external trigeminal nerve stimulation or any other treatment they currently use and may still participate in the registry. There are no clinic or research visits, as the registry is entirely online. Participants will be asked to complete up to six 15- 20-minute surveys over a time period of up to 12 months.

Machine Learning in Guiding rTMS Treatment for GWI-Related Headaches and Body Pain

The goal of this clinical trial is to create a machine learning algorithm to improve active repetitive transcranial magnetic stimulation (rTMS) treatments for veterans and/or active military personnel by alleviating Gulf War Illness related headaches and body pain (GWI-HAP). This study aims to develop and validate a Support Vector Machine (SVM) model that could replace the trial-and-error process by assessing functional connectivity provided by resting state functional magnetic resonance imaging (rs-fMRI) data to predict the most effective rTMS protocol for each person. All participants will be receiving active rTMS treatment. The main questions it intends to answer are: 1. Does the SVM model predict a more effective treatment response rate for predicted respondents undergoing active rTMS at the left dorsolateral prefrontal cortex (DLPFC) compared to predicted non-respondents? 2. Does the SVM model predict a more effective treatment response rate while undergoing active rTMS at the left dorsolateral prefrontal cortex (DLPFC) and left motor cortex (LMC) in predicted respondents compared to predicted non-respondents? Participants will undergo the following: 1. Receive a total of 13 active rTMS treatment sessions over 3-4 months. 2. Visit the clinic for a total of 15 visits for assessments, check ups, and treatments. 3. Keep a daily log of their headaches, muscle and joint pain throughout the study.

Treatment Response in Patients With Medication-Overuse Headache

The aim of this study to evaluate pre-injection patient-related factors that may influence treatment response in patients with medication-overuse headache who underwent ultrasound-guided greater occipital nerve block.

Efficacy and Safety of Transcutaneous Auricular Vagus Nerve Stimulation for Postoperative Headache Following Stent-Assisted Coiling of Unruptured Intracranial Aneurysms

The goal of this clinical trial is to evaluate the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) in reducing postoperative headache among adults undergoing stent-assisted coiling for unruptured intracranial aneurysms (UIAs). The study will include male and female participants aged 18 to 80 years who are scheduled for endovascular treatment of UIAs with stent-assisted coiling or flow diverter devices. The main questions it aims to answer are: * Can taVNS reduce the incidence of headache within 90 days after stent-assisted embolization of UIAs? * Is taVNS safe and well-tolerated in this patient population? Researchers will compare patients receiving active taVNS to those receiving sham stimulation to determine if taVNS leads to fewer postoperative headaches and reduced need for analgesic medications. Participants will: * Wear a taVNS device on the left earlobe (active group) or cymba conchae (sham group) starting 1 day before the procedure * Receive 30-minute stimulation sessions, twice daily, until postoperative day 5 * Undergo follow-up assessments of headache occurrence, pain intensity, analgesic use, and any adverse events through day 90 after the procedure

The Effectiveness of CBD and CBN in the Treatment of Facial Pain and Headache of Muscular Origin

The aim of the study is to evaluate the effectiveness of an aqueous solution containing CBD and CBN in the management of Facial Pain and Headache of Muscular Origin. A randomized (block randomization), double-blind, two-arm controlled trial will involve 42 adult patients diagnosed with Facial Pain and Headache of Muscular Origin which is lasting more than 3 months on the basis of clinical examination. Qualified study participants will be randomly assigned to two groups. The studied group will receive tan aqueous solution containing CBD and CBN, to drink at home in the dose determined by the attending physician, while the control group will receive an aqueous solution of placebo, to drink at home in the dose determined by the attending physician during this time. Each subject will be tested on the qualification day (D0), on 20 days after D0 (D20), and then 40 (D40) and 60 (D60) days after the qualification day using electromyography (EMG), pressure pain threshold test (PPT), clinical examination and surveys.