Migraine Medication Effects on Urinary Symptoms

• Conditions: Bladder Pain Syndrome; Migraine Disorders; Migraine; Overactive Bladder; Overactive Bladder Syndrome; Overactive Detrusor; Interstitial Cystitis
• Interventions: Drug: Ubrogepant; Drug: Botulinum toxin A; Drug: Rimegepant; Drug: Atogepant; Drug: Eptinezumab; Drug: Fremanezumab; Drug: Galcanezumab; Drug: Erenumab

• Registration Number: NCT06212661
• Lead Sponsor: The Cleveland Clinic

Brief Summary

A prospective observational cohort trial to study the effects of CGRP inhibitors (CGRPi) on lower urinary tract symptoms (LUTS) and bladder/pelvic pain. Candidates for either CGRPi or an alternative therapy for refractory migraines (OnabotulinumtoxinA (BoNTA) extracranial muscle injections) with baseline LUTS will be recruited. The investigators will assess LUTS and pelvic pain using validated symptom and quality-of-life questionnaires, pretreatment and at 3 months post-treatment follow-up, comparing change in symptoms based on treatment received.

Detailed Description

Common urinary urgency syndromes may be related to over-activation of bladder afferent pathways involving CGRP signaling. CGRP (calcitonin gene related protein) is a neurotransmitter in afferent pathways also involved in central nociception and hypersensitization. CGRP-targeted therapies, approved for migraine treatment, have the potential to alleviate lower urinary tract symptoms, but these possible effects have not been studied in humans.

This is a prospective observational cohort trial to study the effects of CGRP inhibitors (CGRPi) on lower urinary tract symptoms (LUTS) and bladder/pelvic pain. Candidates for either CGRPi or an alternative therapy for refractory migraines (OnabotulinumtoxinA (BoNTA) extracranial muscle injections) with baseline LUTS will be recruited. The investigators will assess LUTS and pelvic pain using validated symptom and quality-of-life questionnaires, pretreatment and at 3 months post-treatment follow-up, comparing change in symptoms based on treatment received.

Study Timeline

• Study First Submitted: 2024-01-09
• Study First Submitted QC: 2024-01-09
• Study First Posted: 2024-01-19
• Study Start: 2024-04-05
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-14
• Last Update Posted: 2024-05-16
• Primary Completion: 2025-05
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: Female
• Target Recruitment: 200

Inclusion Criteria

• Female Patients > 18 years

• Refractory migraine, planned treatment with either:

• CGRP inhibitors, including:

  • CGRP small molecule receptor antagonists ("gepants"): Ubrogepant, Rimegepant, Atogepant.
  • CGRP monoclonal antibodies: Eptinezumab, Fremanezumab, Galcanezumab.
  • CGRP receptor monoclonal antibodies: Erenumab.

• BoNTA extracranial muscle injections

• Any of the following symptoms during the last month:

  • Urinating too often (frequency).
  • Having a sudden urge to urinate that's difficult to hold back (urgency).
  • Having a sudden urge to urinate and urine leaking before you make it to the toilet (urge incontinence).

Exclusion Criteria

• Age < 18 years
• CGRP treatment within the last 12 months or BoNTA (head / bladder) last 6 months.
• Patient (or medical decision-maker) unable to provide informed consent or unable to answer questionnaire.
• Unable to urinate, eg: post cystectomy, indwelling catheter, on intermittent self catheterization, ESRD w/ anuria.
• Prior bladder BoNTA in last 12 months.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CGRP inhibitor	Ubrogepant	* Ubrogepant (Ubrelvy™) * Rimegepant (Nurtec®) * Atogepant (Qulipta™) * Eptinezumab (Vyepti®) * Fremanezumab (Ajovy®) * Galcanezumab (Emgality®) * Erenumab (Aimovig®) dosage and duration according to provider's clinical decision.
CGRP inhibitor	Rimegepant	* Ubrogepant (Ubrelvy™) * Rimegepant (Nurtec®) * Atogepant (Qulipta™) * Eptinezumab (Vyepti®) * Fremanezumab (Ajovy®) * Galcanezumab (Emgality®) * Erenumab (Aimovig®) dosage and duration according to provider's clinical decision.
CGRP inhibitor	Fremanezumab	* Ubrogepant (Ubrelvy™) * Rimegepant (Nurtec®) * Atogepant (Qulipta™) * Eptinezumab (Vyepti®) * Fremanezumab (Ajovy®) * Galcanezumab (Emgality®) * Erenumab (Aimovig®) dosage and duration according to provider's clinical decision.
CGRP inhibitor	Eptinezumab	* Ubrogepant (Ubrelvy™) * Rimegepant (Nurtec®) * Atogepant (Qulipta™) * Eptinezumab (Vyepti®) * Fremanezumab (Ajovy®) * Galcanezumab (Emgality®) * Erenumab (Aimovig®) dosage and duration according to provider's clinical decision.
CGRP inhibitor	Atogepant	* Ubrogepant (Ubrelvy™) * Rimegepant (Nurtec®) * Atogepant (Qulipta™) * Eptinezumab (Vyepti®) * Fremanezumab (Ajovy®) * Galcanezumab (Emgality®) * Erenumab (Aimovig®) dosage and duration according to provider's clinical decision.
CGRP inhibitor	Galcanezumab	* Ubrogepant (Ubrelvy™) * Rimegepant (Nurtec®) * Atogepant (Qulipta™) * Eptinezumab (Vyepti®) * Fremanezumab (Ajovy®) * Galcanezumab (Emgality®) * Erenumab (Aimovig®) dosage and duration according to provider's clinical decision.
CGRP inhibitor	Erenumab	* Ubrogepant (Ubrelvy™) * Rimegepant (Nurtec®) * Atogepant (Qulipta™) * Eptinezumab (Vyepti®) * Fremanezumab (Ajovy®) * Galcanezumab (Emgality®) * Erenumab (Aimovig®) dosage and duration according to provider's clinical decision.
BoNTA extracranial muscle injections	Botulinum toxin A	Botolinum toxin A (Botox) Injection into extracranial muscles to treat migraine. Dosage and duration according to provider's clinical decision

Primary Outcome Measures

Name	Time	Method
changes in OAB symptoms	3 months	To prospectively compare changes in OAB symptoms after beginning CGRP inhibitor treatment for migraine, with changes after beginning local BoNTA injections for migraine as controls.; OAB symptom change will be measured using the International Consultation on Incontinence Questionnaire (ICIQ) - Female Lower Urinary Tract Symptoms (FLUTS). ICIQ-FLUTS questionnaire composite OAB score, including urgency, frequency, nocturia and urge incontinence domains (range: 0-16, higher scores indicate worse symptoms). Differences of 2-4 points with a standard deviation of 3-4 points were reported as significant in the literature.

Secondary Outcome Measures

Name	Time	Method
changes in bladder pain symptoms	3 months	To prospectively compare changes in bladder pain symptoms after beginning CGRP inhibitor treatment for migraine, with changes after beginning local BoNTA injections for migraine as controls.; Bladder / pelvic pain symptom change will be measured using the Female Genitourinary Pain Index (GUPI). The score ranges from 0 to 39, quality of life question score from 0 to 6, and higher scores indicate worse symptoms.
rates of LUTS and LUTS-related quality of life (QoL) in patients with chronic refractory migraine.	3 months	To assess rates of LUTS (Lower Urinary Tract Symptoms) and LUTS-related quality of life (QoL) in patients with chronic refractory migraine.; LUTS will be assessed using the International Consultation on Incontinence Questionnaire (ICIQ) - Female Lower Urinary Tract Symptoms (FLUTS). This questionnaire has 12 symptoms questions scored 0 to 4, overall questionnaire score is 0 to 48 points, and higher scores indicate worse symptoms.; Bladder / pelvic pain symptoms will be measured using the Female Genitourinary Pain Index (GUPI). The score ranges from 0 to 39, higher scores indicate worse symptoms.; LUTS-related quality of life question, adopted from the international prostate symptom score (IPSS) or American Urological Association symptom index (AUASI), is scored 0 to 6 and a higher score indicated worse quality of life.

Trial Locations

Locations (1)

Cleveland Clinic, Main Campus; 🇺🇸 Cleveland, Ohio, United States