Effects of oxytocin receptor antagonization in migraine: A randomized, double-blind, placebo-controlled human provocation study
Organizational Data
- DRKS-ID:
- DRKS00033341
- Recruitment Status:
- Recruiting planned
- Date of registration in DRKS:
- 2024-01-08
- Last update in DRKS:
- 2024-01-08
- Registration type:
- Prospective
Acronym/abbreviation of the study
oxytocin and migraine
URL of the study
No Entry
Brief summary in lay language
No Entry
Brief summary in scientific language
This study delves into the complex relationship between hormones, specifically oxytocin, and migraine attacks. Migraine, affecting 15% of the global population, poses a significant health burden, especially for women. Hormonal fluctuations, especially during menstruation, have been associated with triggering migraines. While the focus was historically on estrogen, attention has now shifted to alternative hormones, with oxytocin emerging as a key player. In this placebo-controlled, double-blind, randomized human provocation study using a commercially available oxytocin receptor antagonist (atosiban), our goal is to investigate the impact of inhibiting oxytocin as a migraine trigger and understand the underlying pathophysiological pathways involved in migraine. We hypothesize that an inhibited effect of oxytocin due to receptor antagonism will lead to migraine-like attacks in women with migraine. Beyond examining oxytocin antagonization as a trigger for migraine attacks, our study seeks to uncover the underlying mechanisms by exploring its impact on vascular parameters and serological migraine biomarkers, such as calcitonin gene-related peptide (CGRP). Continuous hormonal contraception is implemented as an inclusion criteria to minimize the influence of fluctuating sex hormones. A control group of men with migraines is included to assess sex-specific impacts. Previous human provocation studies indicate that only individuals with migraines experience provoked attacks, while healthy volunteers, at most, develop a mild headache. Therefore, another control group comprisin healthy women without migraine using a continuous hormonal contraception will be included. Both control groups will undergo the same study protocol. In summary, this investigation seeks to advance our understanding of hormone-dependent aspects of migraine pathophysiology, potentially paving the way for innovative therapeutic interventions centered around the oxytocin pathway.
Health condition or problem studied
- ICD10:
- G43.0 - Migraine without aura [common migraine]
- Healthy volunteers:
- Yes
Interventions, Observational Groups
- Arm 1:
- Women with migraine using continuous hormonal contraception. Participants will receive an intravenous infusion of atosiban (6.75mg, equivalent to 0.9ml, as a bolus over 1 minute, followed by an additional 30.75mg, equivalent to 4.1ml, over 1.5 hours) or placebo (0.9ml NaCl as a bolus over 1 minute, followed by 4.1ml NaCl/min over 1.5 hours) via a peripheral intravenous access in the cubital vein. Following the cross-over design, patients who received atosiban at the first visit will receive placebo at the second visit, and vice versa. There must be a minimum of 7 days between the first and second visits.
- Arm 2:
- Men with migraine. Participants will receive an intravenous infusion of atosiban (6.75mg, equivalent to 0.9ml, as a bolus over 1 minute, followed by an additional 30.75mg, equivalent to 4.1ml, over 1.5 hours) or placebo (0.9ml NaCl as a bolus over 1 minute, followed by 4.1ml NaCl/min over 1.5 hours) via a peripheral intravenous access in the cubital vein. Following the cross-over design, patients who received atosiban at the first visit will receive placebo at the second visit, and vice versa. There must be a minimum of 7 days between the first and second visits.
- Arm 3:
- Healthy women using continuous hormonal contraception. Participants will receive an intravenous infusion of atosiban (6.75mg, equivalent to 0.9ml, as a bolus over 1 minute, followed by an additional 30.75mg, equivalent to 4.1ml, over 1.5 hours) or placebo (0.9ml NaCl as a bolus over 1 minute, followed by 4.1ml NaCl/min over 1.5 hours) via a peripheral intravenous access in the cubital vein. Following the cross-over design, patients who received atosiban at the first visit will receive placebo at the second visit, and vice versa. There must be a minimum of 7 days between the first and second visits.
Endpoints
- Primary outcome:
- Incidence of migraine-like attacks within a 12-hour observation period following administration of atosiban vs. placebo in women with migraine using continuous hormonal contraception.
- Secondary outcome:
- Incidence of headache attacks (all kinds) within a 12-hour observation period following administration of atosiban vs. placebo in women with migraine under continuous hormonal contraception / men with migraine / healthy female controls under continuous hormonal contraception. Headache intensity within a 12-hour observation period following administration of atosiban vs. placebo in women with migraine under continuous hormonal contraception / men with migraine / healthy female controls under continuous hormonal contraception. Changes in mean arterial blood pressure following administration of atosiban vs. placebo in women with migraine under continuous hormonal contraception / men with migraine / healthy female controls under continuous hormonal contraception, calculated as the area under the curve (AUC) between baseline and 180 minutes after migraine induction. Changes in mean heart rate following administration of atosiban vs. placebo in women with migraine under continuous hormonal contraception / men with migraine / healthy female controls under continuous hormonal contraception, calculated as the AUC between baseline and 180 minutes after migraine induction. Changes in the diameter of the superficial temporal artery following administration of atosiban vs. placebo in women with migraine under continuous hormonal contraception / men with migraine / healthy female controls under continuous hormonal contraception, calculated as the AUC between baseline and 180 minutes after migraine induction. Changes in blood flow velocity of the middle cerebral artery following administration of atosiban vs. placebo in women with migraine under continuous hormonal contraception / men with migraine / healthy female controls under continuous hormonal contraception, calculated as the AUC between baseline and 180 minutes after migraine induction. Changes in CGRP levels in saliva following administration of atosiban vs. placebo in women with migraine under continuous hormonal contraception / men with migraine / healthy female controls under continuous hormonal contraception, calculated as the AUC between baseline and 180 minutes after migraine induction.
Study Design
- Purpose:
- Other
- Allocation:
- Randomized controlled study
- Control:
-
- Placebo
- Phase:
- N/A
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- Yes
- Assignment:
- Crossover
- Sequence generation:
- No Entry
- Who is blinded:
-
- Investigator/therapist
- Patient/subject
Recruitment
- Recruitment Status:
- Recruiting planned
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Monocenter study
- Recruitment location(s):
-
- University medical center Charité Universitätsmedizin Berlin Berlin
Recruitment period and number of participants
- Planned study start date:
- 2024-07-01
- Actual study start date:
- No Entry
- Planned study completion date:
- 2026-03-02
- Actual Study Completion Date:
- No Entry
- Target Sample Size:
- 60
- Final Sample Size:
- No Entry
Inclusion Criteria
- Sex:
- All
- Minimum Age:
- 18 Years
- Maximum Age:
- 45 Years
- Additional Inclusion Criteria:
- Group 1: Women with migraine are eligible to be included in the study if all of the following criteria apply: 1. Confirmed episodic migraine based on the criteria of the IHS 2. 1-5 migraine days in the 28 days prior to study enrollment 3. Use of continuous hormonal contraception (i.e., no hormone-free interval) for at least 3 months 4. Age 18-45 years upon entry into screening. Control 1: Men with migraine are eligible to be included in the study if all of the following criteria apply: 1. Confirmed episodic migraine based on the criteria of the International Headache Society (IHS) 1. 1-5 migraine days in the 28 days prior to study enrollment 2. Age 18-45 years upon entry into screening. Control 2: Healthy female controls are eligible to be included in the study if all of the following criteria apply: 1. Use of continuous hormonal contraception (i.e., no hormone-free interval) for at least 3 months 2. Age 18-45 years upon entry into screening.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply: 1. History of any primary headache disorder other than migraine without aura (for participants with migraine), or tension-type headache with a frequency of <5 headache days per month before screening according to the IHS criteria, based on medical records and/or patient self-report. 2. History of any secondary headache disorder before screening, based on medical records and/or patient self-report. 3. Intake of prophylactic migraine medication within ≤30 days or 5 plasma half-lives (whichever is longer) prior to screening. 4. Intake of hormonal treatments other than hormonal contraception. 3. History or evidence of neurological disorders (e.g., multiple sclerosis, brain tumor, history of severe traumatic brain injury, history of brain surgery). 4. History or evidence of severe inflammatory diseases (infectious, rheumatic). 5. Evidence of arterial hypertension. 6. History or evidence of cardiovascular diseases (e.g., cerebral ischemia, coronary heart disease, history of myocardial infarction, peripheral arterial disease, severe heart valve disease). 7. Evidence of Diabetes mellitus. 8. Body Mass Index <18 or >30 kg/m2. 9. Female participants who are pregnant or breastfeeding or plan to become pregnant or breastfeed during participation in the study. 10. History or evidence of severe psychiatric disorders. 11. Previous participation in a provocation study. 12. Initiation of any new medical treatment and/or device during study period results in exclusion. 13. Participants likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participants’ and investigator’s knowledge.
Addresses
Primary Sponsor
- Address:
- Charité Universtitätsmedizin BerlinDr. med. Bianca Raffaelli10117 BerlinGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Charité Universitätsmedizin BerlinDr. med. Bianca RaffaelliCharitéplatz 110117 BerlinGermany
- Telephone:
- +49 30 450 660 888
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Contact for Public Queries
- Address:
- Charité Universitätsmedizin BerlinDr. med. Bianca RaffaelliCharitéplatz 110117 BerlinGermany
- Telephone:
- +49 30 450 660 888
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Principal Investigator
- Address:
- Charité Universitätsmedizin BerlinDr. med. Bianca RaffaelliCharitéplatz 110117 BerlinGermany
- Telephone:
- +49 30 450 660 888
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Sources of Monetary or Material Support
Institutional budget, no external funding (budget of sponsor/PI)
- Address:
- Charité Universtitätsmedizin Berlin10117 BerlinGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Ethics Committee
Address Ethics Committee
- Address:
- Ethikkommission der Charité – Universitätsmedizin BerlinCharitéplatz 110117 BerlinGermany
- Telephone:
- (+49)30-450517222
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://ethikkommission.charite.de
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2023-10-12
- Ethics committee number:
- EA1/268/23
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2023-12-18
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- No Entry
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry