Impact of Combined Oral Contraceptive Pills on Migraine

Impact of Combined Oral Contraceptive Pills on Migraine, a Randomized Controlled Trial

The investigators will assess the effect of combined oral contraceptive pills (COCs) on migraine features and treatment response to allow better interpretation of the exact consequence of hormonal contraceptive use on migraineurs.

Study Overview

• Status: Recruiting
• Conditions: Migraine
• Intervention / Treatment: Drug: Combined oral contraceptive; Drug: Vaginal Ring

Detailed Description

The investigators will use a questionnaire to detect the migraineur demographic and clinical features (disease duration, attack frequency and duration, pain intensity assessed by visual analogic scale, HIT score in female patients on regular COCs

• Special emphasis was put on clinical phenotype (for example, the character of pain, location, associated symptoms, etc.); vascular risk factors (hypertension, diabetes, smoking); history of cerebrovascular events and other conditions (collagen disorders, hepatic disorders, blood diseases, heart, kidneys), and family history.
• All the patients will undergo clinical neurological and general physical examinations, and migraine history and associated phenotypic features will be established.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: mohamed G. Zeinhom, MD; Phone Number: 2001009606828; Email: mohamed_gomaa@med.kfs.edu.eg
• Study Contact Backup: Name: sherihan R. ahmed, MD; Phone Number: 2001113432342; Email: sherihan_rezq@med.kfs.edu.eg

Study Locations

• Egypt
  • Kafr Ash Shaykh, Egypt, 33511
    • Recruiting
    • Kafr Elsheikh University Hospital
    • Contact: mohamed G. Zeinhom, MD; Phone Number: 2001009606828; Email: mohamed_gomaa@med.kfs.edu.eg
    • Contact: sherihan R. ahmed, MD; Phone Number: 2001007481842; Email: sherihan_rezq@med.kfs.edu.eg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• female migraine patients on COCs or mechanical contraceptive methods, according to the International Classification of Headache Disorders 3rd edition, aged 18-55 years

Exclusion Criteria:

1. Patients with major neurological conditions such as (epilepsy, ischemic or hemorrhagic stroke, multiple sclerosis, mitochondrial diseases, and brain tumors).
2. pregnant, lactating, and menopausal patients.
3. Patients with any contraindications to ibuprofen or propranolol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: the COCs group; The arm will include 200 migraine patients diagnosed according to ICHD3-beta criteria. The patients are regular users of COCs and will receive propranolol 80-160mg daily and ibuprofen 200-400 mg only in acute migraine attacks for 3 months. We will assess The change in migraine days per 28 days, the number of migraine days after three months of treatment, and the percentage of patients who achieved ≥ 50% reduction in the monthly headache days frequency compared to the baseline frequency. HIT-6 score reduction in each group after three months of treatment. The safety of treatment was evaluated by monitoring and documenting treatment-emergent adverse events (TEAE) in patients through regular follow-up procedures for three months. We will assess the phenotypic features of migraine.	Drug: Combined oral contraceptive; The arm will include 200 migraine patients diagnosed according to ICHD3-beta criteria. The patients are regular users of COCs and will receive propranolol 80-160mg daily and ibuprofen 200-400 mg only in acute migraine attacks for 3 months.
Active Comparator: the non-hormonal contraception group; The arm will include 200 migraine patients diagnosed according to ICHD3-beta criteria. The patients are not receiving any hormonal contraception and will receive propranolol 80-160mg daily and ibuprofen 200-400 mg only in acute migraine attacks for 3 months. We will assess The change in migraine days per 28 days, the number of migraine days after three months of treatment, and the percentage of patients who achieved ≥ 50% reduction in the monthly headache days frequency compared to the baseline frequency. HIT-6 score reduction in each group after three months of treatment. The safety of treatment was evaluated by monitoring and documenting treatment-emergent adverse events (TEAE) in patients through regular follow-up procedures for three months. We will assess the phenotypic features of migraine.	Drug: Vaginal Ring; The arm will include 200 migraine patients diagnosed according to ICHD3-beta criteria. The patients are users of mechanical contraceptive methods and will receive propranolol 80-160mg daily and ibuprofen 200-400 mg only in acute migraine attacks for 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of patients who achieved ≥ 50% change in the monthly migraine days frequency compared to the baseline frequency	We will assess The percentage of patients who achieved ≥ 50% change in the monthly headache days frequency compared to the baseline frequency in each group	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIT-6 score change in each group after three months of treatment	The investigators assessed the absolute change in HIT6 score, the Headache Impact Test-6 (HIT-6) assessed the burden of headache in each group; the HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress, the patient answers each of the six related questions using one of the following five responses: "never", "rarely", "sometimes", "very often," or "always." These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent. It has four impact grades: little-to-no impact (HIT-6 score: 36-49), moderate impact (HIT-6 score: 50-55), substantial impact (HIT-6 score: 56-59), and severe impact (HIT-6 score: 60-78)	3 months
The duration of migraine attack in hours after three months of treatment	After three months of treatment, the investigators will assess the duration of migraine attacks in hours in each group	3 months
The severity of migraine attack on VAS score after three months of treatment	After three months of treatment, the investigators will assess the severity of migraine attacks on VAS scores. VAS is a scale from one to ten where one is the least severe pain while ten is the most severest pain	3 months
The monthly migraine days per month	The investigators will assess the change in migraine days per month in each group	3 months
percentage of phenotypic features after three months of treatment	After three months of treatment, the investigators will assess percentage of phenotypic features in each group.	3 months

Collaborators and Investigators

• Sponsor: Kafrelsheikh University

Publications and helpful links

General Publications

• Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF. Migraine in the United States: epidemiology and patterns of health care use. Neurology. 2002 Mar 26;58(6):885-94. doi: 10.1212/wnl.58.6.885.
• Lipton RB, Liberman JN, Kolodner KB, Bigal ME, Dowson A, Stewart WF. Migraine headache disability and health-related quality-of-life: a population-based case-control study from England. Cephalalgia. 2003 Jul;23(6):441-50. doi: 10.1046/j.1468-2982.2003.00546.x.
• Mushet GR, Miller D, Clements B, Pait G, Gutterman DL. Impact of sumatriptan on workplace productivity, nonwork activities, and health-related quality of life among hospital employees with migraine. Headache. 1996 Mar;36(3):137-43. doi: 10.1046/j.1526-4610.1996.3603137.x.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2024
• Primary Completion (Estimated): May 15, 2025
• Study Completion (Estimated): July 30, 2025

Study Registration Dates

• First Submitted: July 13, 2024
• First Submitted That Met QC Criteria: July 13, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Estimated): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: migraine; Egypt; combined oral contraception
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Combined
• Other Study ID Numbers: 091287

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All the data supporting this research's findings may be available from Sherihan R.Ahmed, upon reasonable request

Drug and device information, study documents

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