Axert

Migraine and Fibromyalgia (FM) are chronic pain disorders characterized by altered central pain processing and impaired endogenous pain inhibition. FM presents with widespread musculoskeletal pain, fatigue, sleep disturbance, and cognitive symptoms and is strongly associated with central sensitization. Migraine similarly involves dysfunction of central inhibitory and descending pain modulation, with evidence of abnormal cortical excitability, impaired sensory habituation, and alterations in pain-related evoked potentials. Conditioned Pain Modulation (CPM) is a measure of the body's endogenous pain-inhibitory mechanism, based on the phenomenon whereby the pain evoked by one painful stimulus (the test stimulus) is reduced by the concurrent application of a second, remote nociceptive stimulus (the conditioning stimulus). It is widely regarded as a proxy for the function of descending pain-modulatory pathways. CPM is used as an experimental biomarker of descending pain inhibition across chronic pain conditions, including fibromyalgia and migraine. Studies consistently demonstrate reduced inhibitory responses in both migraine and fibromyalgia compared with healthy controls, indicating a robust deficit in descending pain modulatory systems. Combining a contact heat test stimulus (TS) with a cold pressor conditioning stimulus (CS) is a widely used and validated CPM paradigm. Nerivio, a Remote Electrical Neuromodulation (REN) device, is a non-invasive, non-pharmacological therapy indicated for the acute and preventive treatment of migraine. The REN device is worn on the upper arm and delivers peripheral electrical stimulation to activate CPM-related descending inhibitory pathways and reduce migraine pain. This distal stimulation approach is designed to activate CPM-related circuits by recruiting brainstem pain-regulatory centers and modulating central nociceptive processing. This randomized, double-blind, placebo-controlled trial is designed to assess the effect of a single REN session on CPM and cortical pain processing in adults with migraine or fibromyalgia. Using a standardized CPM induction protocol, the study will evaluate changes in behavioral CPM responses, before, during, and after REN vs. sham stimulation in patients with migraine or fibromyalgia. This study aims to clarify whether REN enhances descending pain inhibition and pain processing in populations with impaired endogenous pain modulation.

This is a double-blind, randomized, multicenter, outpatient evaluation of the safety and efficacy of elismetrep, as compared with placebo, in the treatment of moderate or severe of migraine.

The current study will evaluate effectiveness of cognitive behavioral therapy for migraine compared to migraine education (ME) to improve migraine-related quality of life in the real-world setting of the Veterans Health Administration (VHA).

Background \& Rationale: One in ten Canadian youth have migraine, a disabling neurological disease that is more common in females and characterized by moderate-severe disabling headaches. Migraine attacks occur in a cycle that begins with a prodromal phase, followed by aura, a pain phase (headache), and finally a postdrome phase when the pain is resolved but other symptoms persist. The prodrome is recognized by \~90% of all youth with migraine, occurs up to 24 hours before headache onset, and consists of a variety of symptoms including, but not limited to, food cravings, fatigue, yawning, mood changes, and sensory hypersensitivity (e.g., light sensitivity). Prodromal symptoms are disabling and frequently graded as moderate to severe. All acute migraine treatments for youth have been studied for use in the pain phase, with the greatest treatment success early in this phase. Unfortunately, only \~1/3 of youth achieve pain freedom within two hours. Recently, a groundbreaking trial found that treatment during the prodrome could prevent the pain phase, although prodromal treatment does not exist for youth. In considering the most innovative, safe, and patient-centered prodromal intervention, remote electrical neuromodulation (REN) is the obvious choice. The investigator's engagement with 175 youth with migraine and their caregivers shows that REN is preferred when pill-based interventions are ineffective or impractical. REN has none of the limitations of pill-based prodromal treatment. The REN device is wearable, battery-operated, worn on the upper arm, and controlled wirelessly by a smartphone application. REN electrically stimulates sensory nerves in the arm below their perceived pain thresholds, but above their depolarization thresholds, to induce a conditioned pain modulation response in the brain to modulate incoming migraine pain signals. Clinical trial and observational studies in youth with migraine have shown REN's safety and efficacy for home-based treatment during the pain phase and led the FDA to clear its use in youth \>8 years. In the adolescent trial, 71% of participants had pain relief at two hours, there were no serious adverse events (AE), and only one device-related AE (transient arm pain) occurred. Also, emerging data show that adults with migraine in the prodrome phase display pain facilitation due to a deficit in pain modulation. Thus, REN's mechanism of action is likely to be more effective during the prodrome vs. the pain phase as it can "turn on" deficient pain modulatory areas earlier when they are most impaired. Research Question \& Objectives: The investigators aim to determine the feasibility of implementing REN treatment during the prodrome to prevent migraine pain in youth with migraine, and hypothesize that: 1. trial design will be feasible 2. REN will be feasible for prodromal treatment, with \>80% of participants using their assigned device to treat a qualifying prodrome. The following feasibility and acceptability outcomes will be measured: 1. proportion of eligible youth that are enrolled into the screening period, subsequently randomized, and treat a qualifying prodrome with REN. 2. recruitment rate, retention, and withdrawals. 3. participant feedback. All secondary outcomes will be reported descriptively, and adverse events will be recorded and reported. Methods: This study will be a pilot randomized, single centre, double-blind, parallel group, sham-controlled trial comparing active to sham REN for the prevention of headache within 24 hours of treating prodromal symptoms in youth with migraine. Participants will be recruited from headache and neurology clinics at the Alberta Children's Hospital. Eligible and consenting participants will complete an intake visit and enter a 60-day screening period where they will complete electronic daily diaries to determine prodrome or headache occurrence and features. Participants with 3-28 qualifying prodromes during screening, where \>75% are followed by a headache within 6 hours, will be randomized 1:1 to treat one qualifying prodrome with active or sham REN over a 60-day treatment period. Participants will be trained on device use and will be instructed to not use any co-interventions during the qualifying prodrome; if headache onsets after the prodrome, participants will be instructed to use their typical acute treatment. During the treated prodrome, a survey will determine the presence, type, and number of prodromal symptoms. Surveys at 2, 24, and 48 hours post-treatment will record the presence or absence of headache, its characteristics, and AEs. The randomization sequence will be prepared by a biostatistician and will follow randomly ordered blocks of four and six, with variable block sizes. Only research pharmacists will have access to this sequence to prepare consecutively numbered blinded and matched study kits. These kits will contain a restricted mobile phone with only the REN software application pre-installed.

Use of a headache journal/calendar in patients who have migraine to ascertain if keeping a headache journal affects the quality of life and the headache burden.

Prospective, single-site, open-label, non-controlled pilot study consisting of two parallel trials. Participants will receive rimegepant or zavegepant for acute migraine treatment during a single Emergency Department visit, with post-discharge follow-up through 28 days. Participants will be allocated to either the rimegepant trial or the zavegepant trial. The study design does not include a placebo or active comparator control group, and the two gepant study drugs are not designed to function as active comparator groups. The objective in this investigation is to examine relief from either rimegepant or zavegepant in separate parallel trials.

This study is testing an investigational inhaled migraine medication to see how well it works, how safe it is, and how well people tolerate it. Adults with migraine will receive both the study medication (ASY202) and a placebo (inactive treatment) at different times during the study. Neither participants nor study staff will know which treatment is given at the time. The medication is taken using a handheld dry powder inhaler to treat migraine attacks when they occur. Following screening, eligible participants will be enrolled and randomized to one of two treatments sequences i.e. one treatment sequence will receive ASY202 in treatment period 1 followed by placebo in treatment period 2 and other treatment sequence will receive placebo in treatment period 1 followed by ASY202 in treatment period 2. The study lasts about 16 weeks and includes a screening period, two treatment periods (with a minimum of 7 days washout period between the treatment periods), and a safety follow-up visit.

This is a double-blind, randomized, multicenter, outpatient evaluation of the efficacy, safety, and tolerability of elismetrep, as compared with placebo, in the acute treatment of migraine.

This study evaluates the clinical effectiveness of the Enso for Migraine program, a comprehensive digital care program combining an FDA-cleared neuromodulation wearable device (Enso), personalized exercise therapy, and a dedicated care team, in reducing migraine frequency among adults with episodic or chronic migraine.

The purpose of this study is to evaluate the impact of the Migraceutics® phase-specific dietary supplement regimen on quality of life, work productivity, and biomarkers in adult migraineurs.

This study will evaluate the efficacy and safety of EVO756 against placebo in adults with migraine.

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