Chordate System Prophylactic Migraine Clinical Investigation

Study Overview
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Brief Summary
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The purpose of this pilot study is to evaluate the performance of the Chordate System, in terms of the prophylactic effect and tolerability of treatment in patients diagnosed with migraine.

Detailed Description
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This was a prospective, interventional, randomized, placebo-controlled, double-blind, multi-center clinical investigation of a medical device system. A pilot study in which patients with frequent migraine attacks received intranasal KOS or placebo using the Chordate System S200 on two occasions.

Official Title
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A Randomized, Placebo-controlled, Double-blind, Multi-center Clinical Investigation to Evaluate the Prophylactic Effect and Tolerability of Intranasal Kinetic Oscillation Stimulation (KOS) Using the Chordate System S200 in Migraine Patients

Conditions
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Migraine

Intervention / Treatment
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* Device: Chordate System S200 + CT100 (active treatment)
* Device: Chordate System S200 + CT100 (placebo treatment)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is legally competent, has been informed of the nature, the scope and the relevance of the study, voluntarily agrees to participation and the study's provisions, and has duly signed the Informed Consent Form (ICF). Male or female aged between 18 and 65 years Diagnosed as suffering from migraine with or without aura according to International Headache Society´s (IHS) classification (International Classification of Headache Disorders (ICHD), 3rd edition, beta version) Reported history of 3 to 8 migraine episodes per month during previous 2 months, confirmed during baseline Reported history of at least 48 hours of freedom from headache between migraine attacks, confirmed during baseline Onset of migraine headache occurred before age 50 Reported history of migraine for more than one year Reported stable dose of prophylactic migraine medication(s), if any, during the two months prior to screening (visit 1), and willing and able to maintain stable dose(s) until the three months follow-up (visit 4) Exclusion Criteria: Meeting the ICHD criteria for medication overuse Reported history of 15 or more headache days per month (i.e. headaches of any kind), confirmed during baseline Reported frequency of non-migraine headaches exceeding 6 days per month, confirmed during baseline Unable to distinguish between migraine headaches and other headache types Treatment with Botox received within 6 months of the screening visit, or between the screening and treatment visits Ongoing treatment with implanted stimulator or other implanted device in the head and/or neck region Known pronounced anterior septal deviation, or other known relevant abnormality in the nasal cavity, including bacterial infection and wounds History of sinus surgery, transphenoidal surgery for pituitary or other lesions or cerebrospinal fluid (CSF) rhinorrhea Fitted with a pacemaker/defibrillator Previously treated with therapeutic radiation to the face (that could have influenced the nasal mucosa) Ongoing upper respiratory tract infection or a body temperature >38.5°C (at treatment), or malignancy in the nasal cavity History of regular nose bleeding (epistaxis), or concomitant condition that could cause excessive bleeding, including treatment with the anticoagulant Varan Head injury or open wound that contraindicates use of Chordate Headband Known allergy to polyvinylchloride, a material used in the Catheter, or medicinal liquid paraffin Concurrent condition or risk of non-compliance that, in the investigator's opinion, may affect the interpretation of performance or safety data or which otherwise contraindicates participation in a clinical investigation Any change in migraine prophylaxis the previous two months Pregnant women Participation in a clinical research study within three months of enrolment or planned participation at any time during this clinical investigation Employees of the study site or the sponsor directly involved with the conduct of the study, or immediate family members or any such individuals Headache or migraine episode within the 48 hours prior to the first treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chordate S200 + control module (CT100), active<br>Chordate System S200 giving Kinetic Oscillation Stimulation Treatment for 15 minutes in each nostril | Device: Chordate System S200 + CT100 (active treatment)<br>* Chordate S200 + CT100 (active treatment) gives Kinetic Oscillation Stimulation for 15 minutes to each nostril and by that giving an effect on the autonomic nervous system (ANS).<br>|
| Placebo Comparator: Chordate S200 + control module (CT100), placebo<br>Chordate System S200 giving Kinetic Oscillation Stimulation in placebo mode. Non-inflated and non-vibrating treatment | Device: Chordate System S200 + CT100 (placebo treatment)<br>* Chordate S200 + CT100 (placebo) is used in the same way as Active treatment, but no Kinetic Oscillation Stimulation is given. Catheter is not inflated and no vibration is given.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Number of Migraine Days Per Four Weeks During the Three Months Post Treatment Investigation Duration | A diary was used where patients added information each day on experienced migraine (yes/no). Baseline was defined as any migraine days from Day -29 until Day -1, i.e. the day before first treatment (Day 1). If full time period for baseline or the post treatment period was not documented, number of migraine days was recalculated with the formula: Number of migraine days = (Number of migraine days x 28) / Number of days observed If data was missing for any patient for more than 14 days during any period of interest, that patient was excluded from analysis. The change from baseline in number of migraine days was calculated as follows: Change = number of migraine days per four weeks for the 3 months post treatment period - number of migraine days per four weeks of the baseline period As the difference between the post treatment period and baseline is presented, negative numbers indicate a post treatment decrease in number of migraine days. | From baseline (28 days pre-treatment) to visit 4 (day 98, ± 7 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Number of Migraine Days During the 1st, 2nd and 3rd Month and During the Final Four Weeks of the Three Month Post Treatment Investigation Duration | A diary was used where patients added information each day on experienced migraine (yes/no). Baseline was defined as any migraine days from Day -29 until Day -1, i.e. the day before first treatment (Day 1). If the full time period for either baseline or post treatment period was not documented number of migraine days was recalculated with the formula: Number of migraine days = (Number of migraine days x 28) / Number of days observed If data was missing for any patient for more than 14 days during any period of interest, that patient was excluded from the analysis of that time period. The change from baseline in number of migraine days was calculated as follows: Change = number of migraine days per four weeks for applicable post treatment period - number of migraine days per four weeks of the baseline period As the difference between applicable post treatment period and baseline is presented, negative numbers indicate a post treatment decrease in number of migraine days. | From baseline (28 days pre-treatment) to visit 4 (day 98, ± 7 days) | 
| Responder Rate | Responder defined as a patient with 50% or greater decrease in the number of migraine days per four weeks, for the 1st, 2nd and 3rd month post treatment vs baseline | From baseline (28 days pre-treatment) to visit 4 (day 98, ± 7 days) | 
| Maximum Migraine Pain Intensity During the 1st, 2nd and 3rd Month, the Final 4 Weeks and the Complete Three Month Post Treatment Investigation Duration | A diary was used where patients added information on the maximum pain intensity on each day according to a 4-point categorical scale (none, mild, medium, severe). The maximum documented pain intensity for each patient during each post treatment time period was tabulated for the active treatment and placebo groups. | From baseline (day ≥ - 28 days) to visit 4 (day 98, ± 7 days) | 
| Mean Change From Baseline in Median Migraine Duration (Hours/Day) During the 1st, 2nd and 3rd Month, the Final 4 Weeks and the Complete Three Month Post Treatment Investigation Duration | A diary was used where patients added information each day on the number of hours with migraine. The median migraine duration in hours per day was determined for each patient, for each post treatment time period. Baseline for each patient was defined as the median number of migraine hours/day from Day -29 until Day -1, i.e. the day before the first treatment (Day 1). The change in median migraine hours/day from baseline, for each defined post treatment time period, was then determined and the mean change is presented. As the differences between applicable post treatment period and baseline is presented, negative numbers indicate a post treatment decrease in number of migraine hours/day. | From baseline (28 days pre-treatment) to visit 4 (day 98, ± 7 days) | 
| Change From Baseline in Drug Consumption for Acute Treatment During the Three Month Post Treatment Investigation Duration |  | From baseline (28 days pre-treatment) to visit 4 (day 98, ± 7 days) | 
| Patient's Satisfaction as Measured on Clinical Global Impression Scales (CGI) | Patient satisfaction, evaluated by a clinician, was measured using 8-point clinical global impression (CGI) scores on an improvement scale (CGI-I: compared to condition at baseline, how much has changed: 0 = Not assessed, 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse). | At visit 4 day 98, ± 7 days | 
| Number of Participants With a Change in Disease-specific Quality of Life From Baseline to End of the Three Month Investigation Duration | Number of Participants with a Change in Disease-specific Quality of Life, as measured by EQ-5D-3L, from Baseline (day 0, visit 2 before first treatment) to End of the Three Month Investigation Duration. EQ-5D-3L uses 5 categorical dimensions - motility, self-care, usual activities, pain/discomfort and anxiety/depression, each classified as improved, no change or worsened. | From baseline (day 0, visit 2) to visit 4 (day 98, ± 7 days) | 
| Disease-specific Quality of Life (VAS Pain Scale) From Baseline to End of the Three Month Study Duration | Disease-specific quality of life, as measured by EQ-VAS, at baseline (day 0, visit 2 before first treatment) and at end of the three month study duration after treatment. The EQ VAS is a standard vertical 20 cm visual analogue scale (similar to a thermometer) for recording an individual's rating for their current health-related quality of life state, with a score from 0-100, where a higher score indicates greater pain intensity. | From baseline (day 0, visit 2) to visit 4 (day 98, ± 7 days) |