Cooling to Alleviate Migraine #3 (CALM3)

A Prospective, Double-blind, Sham-controlled, Randomized Clinical Trial to Assess the Safety and Efficacy of the Mi-Helper Device for Acute Treatment of Migraine in an At Home Setting.

This is a prospective, double-blind, sham-controlled, randomized, decentralized trial. This study aims to assess the safety and efficacy of the Mi-Helper transnasal cooling device for acute treatment of migraine in an at home setting.

Adults aged 18 years to 70 years old with a diagnosis of migraine (with or without aura) for at least one year will be recruited for this study.

Study Overview

• Status: Completed
• Conditions: Migraine; Migraine Headache; Migraine With or Without Aura
• Intervention / Treatment: Device: Mi-Helper

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Indian Harbour Beach, Florida, United States, 32937
      • SPRIM Pro

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age of 18 to 70 years, inclusive, of either sex at birth.
2. Lives in the contiguous United States.
3. Self-reported to be able to read and understand English sufficiently to provide electronic Informed Consent.
4. Diagnosis of migraine with or without aura for at least 1 year.
5. Individual experiences 2 to 8 migraine attacks per month documented via migraine eDiary during screening.
6. Migraine onset before 50 years of age, self-reported during screening.
7. Migraine preventive medication unchanged for 4 weeks prior to study enrollment.
8. Stated willingness to comply with all study procedures and availability for the duration of the study.
9. Individuals that own a functioning smartphone device, internet connection (Wi-Fi or data plan) and are willing to download the study app.

Exclusion Criteria:

1. Participant has difficulty distinguishing his or her migraine attacks from other types of headaches such as tension, exertion, cluster, hormonal or sinus headaches.
2. Participant has 15 or more headache days per month reported via migraine eDiary and during screening.
3. Participant using any opioid medication at the time of screening.
4. Participant has received Botox treatment, barbiturates, SPG block, nerve blocks or trigger point injections in the head or neck within the last 4 weeks of screening.
5. Participant lives at an altitude of 2000 meters or more above sea level.
6. Self-reported intolerance to intranasal therapy.
7. Self-reported recurrent epistaxis or chronic rhinosinusitis.
8. Self-reported sinus or intranasal surgery within the last 4 months of screening.
9. Self-reported history of 'complicated migraine or headaches' (i.e., hemiplegic migraine, ophthalmoplegic migraine, migrainous infarction, basilar migraine, post-traumatic headaches, post-concussion syndrome).
10. Known or suspected pregnancy as self-reported by the prospective participant at the time of screening.
11. Prospective participant unable to fully understand the consent process and provide informed consent due to either language barriers or mental capacity.
12. Self-reported diagnosis of alcohol or substance abuse disorder at the time of screening.
13. Participant with active chronic pain syndromes, such as fibromyalgia, chronic pelvic pain, or Complex Regional Pain Syndrome (CRPS); or other pain syndrome like trigeminal neuralgia.
14. Participant with severe uncontrolled psychiatric conditions or significant neurological disorders (other than migraine) that, in the Investigator's opinion, might interfere with study assessments.
15. Failure to adhere to or inability to complete Study App inputs and onboarding activities during the screening period. Participants who are not adherent during the screening period are not eligible for study entry.
16. Participation in a previous clinical study with the Mi-Helper device.
17. Participation in a migraine study or any other interventional clinical study within the3 months prior to screening.
18. Participant has an uncontrolled medical issue at the time of screening.
19. Any condition for which transnasal air flow would be contraindicated, as determined by the Principal Investigator (PI).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (active treatment); 10 liters per minute of dehumidified air administered via Mi-Helper for 15 minutes	Device: Mi-Helper; The Mi-Helper device is a non-invasive, drug-free, novel therapy that uses a patented process of dry air flow across the nasal turbinates to induce a phase change (evaporation) that extracts energy (thermodynamics) causing local cooling which modulates nerves associated with pain and other symptoms of migraine. The device delivers a controlled pressure and flow of dry room temperature air along with a nebulized saline mist for added comfort and evaporative efficiency.
Sham Comparator: Group II (sham); 2 LPM of ambient air administered intermittently via Mi-Helper for 15 minutes	Device: Mi-Helper; The Mi-Helper device is a non-invasive, drug-free, novel therapy that uses a patented process of dry air flow across the nasal turbinates to induce a phase change (evaporation) that extracts energy (thermodynamics) causing local cooling which modulates nerves associated with pain and other symptoms of migraine. The device delivers a controlled pressure and flow of dry room temperature air along with a nebulized saline mist for added comfort and evaporative efficiency.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Freedom at 2 Hours Post Treatment	Proportion of participants with a change in headache severity from mild/moderate/severe pain at baseline to no pain at 2 hours after treatment completion (if rescue medication was not used)	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Relief at 2 Hours Post Treatment	Proportion of participants with a change in headache severity from severe or moderate pain at baseline to mild or no pain at 2 hours post treatment completion, or from mild pain at baseline to no pain no pain at 2 hours after treatment completion (if rescue medication was not used)	2 hours
Sustained Pain Freedom at 24 Hours Post Treatment	Proportion of participants with pain freedom with no administration of rescue medication and with no recurrence of a mild/moderate/severe headache	2-24 Hours
Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post Treatment	Proportion of participants with a change from mild, moderate or severe symptom severity at baseline to none at 2 hours post treatment completion.	2 hours
Participants' Global Impression of Acute Treatment Effect	Measured by the Patient Global Impression of Change (PGIC), on which participants use a 7-point scale, where 1=very much improved to 7=very much worse. Scores of 1 or 2 will be considered successes.	24 Hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Relief Immediately Post Treatment	Proportion of participants with a change in headache severity from severe or moderate pain at baseline to mild or no pain at 0 hours post treatment completion, or from mild pain at baseline to no pain no pain at 0 hours after treatment completion (if rescue medication was not used)	0 minutes
Pain Freedom Immediately Post Treatment	Proportion of participants with a change in headache severity from mild/moderate/severe pain at baseline to no pain at 2 hours after treatment completion (if rescue medication was not used)	0 Hours
Sustained Pain Freedom at 48 Hours Post Treatment	Proportion of participants with pain freedom with no administration of rescue medication and with no recurrence of a mild/moderate/severe headache	2 - 48 Hours
Rescue Medication Use	Use of rescue medication before 2 hours post treatment completion.	2 Hours
Freedom From Most Bothersome Symptom (MBS) at Immediately Post Treatment	Proportion of participants with a change from mild, moderate or severe symptom severity at baseline to none immediately post treatment completion.	0 minutes
Relief From Most Bothersome Symptom (MBS) Immediately Post Treatment	Proportion of participants with a change from severe or moderate symptom severity at baseline to the traditional 4-point Visual Rating Scalemild or none at 0 hours, or from mild symptom severity at baseline to none at 0 hours post treatment completion (based on the traditional 4-point Visual Rating Scale)	0 hours
Freedom From Nausea Immediately Post Treatment	Proportion of participants with a change from mild, moderate or severe symptom severity at baseline to none immediately post treatment completion (based on the traditional 4-point Visual Rating Scale)	0 hours
Freedom From Photophobia Immediately Post Treatment	Proportion of participants with a change from mild, moderate or severe symptom severity at baseline to none ( immediately post treatment completion.	0 Hours
Freedom From Phonophobia Immediately Post Treatment	Proportion of participants with a change from mild, moderate or severe symptom severity at baseline to none immediately post treatment completion.	0 hours
Freedom From Nausea at 2 Hours Post Treatment	A reduction from mild, moderate or severe symptom severity at baseline to none at 2 hours post treatment completion.	2 Hours
Freedom From Photophobia at 2 Hours Post Treatment	Proportion of participants with a change from mild, moderate or severe symptom severity at baseline to none at 2 hours post treatment completion.	2 Hours
Freedom From Phonophobia at 2 Hours Post Treatment	Proportion of participants with a change from mild, moderate or severe symptom severity at baseline to none at 2 hours post treatment completion.	2 Hours

Collaborators and Investigators

• Sponsor: Mi-Helper, Inc.
• Investigators: Principal Investigator: Jessica Ailani, MD, MedStar Georgetown Headache Center

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2025
• Primary Completion (Actual): October 29, 2025
• Study Completion (Actual): December 15, 2025

Study Registration Dates

• First Submitted: March 5, 2025
• First Submitted That Met QC Criteria: March 11, 2025
• First Posted (Actual): March 13, 2025

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Neuromodulation; Device; Decentralized; Neuromodulation device
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: COT-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the final article including results in the text, tables, figures, and appendices, will be made available after deidentification.
• IPD Sharing Time Frame: The data will be made available within 6 months of the study's conclusion and will remain available for at least 3 years.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal to achieve results in line with the proposed outcomes will be able to obtain IPD.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No