Migraine Medication Effects on Urinary Symptoms

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 Overview

• Status: Enrolling by invitation
• Conditions: Overactive Bladder; Migraine; Migraine Disorders; Overactive Detrusor; Interstitial Cystitis; Overactive Bladder Syndrome; Bladder Pain Syndrome
• Intervention / Treatment: Drug: Ubrogepant; Drug: Rimegepant; Drug: Atogepant; Drug: Eptinezumab; Drug: Fremanezumab; Drug: Galcanezumab; Drug: Erenumab; Drug: Botulinum toxin A

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 Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Chen Shenhar, MD; Phone Number: 216.444.5600; Email: shenhac@ccf.org
• Study Contact Backup: Name: Howard B Goldman, MD; Phone Number: 216.312.5421; Email: goldmah@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic, Main Campus
      • Contact: Chen Shenhar, MD; Phone Number: 216-444-5600; Email: shenhac@ccf.org
      • Contact: Howard B Goldman, MD; Phone Number: 216-312-5421; Email: goldmah@ccf.org

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Female patients age 18 years or over, presenting to the neurology outpatient clinics for treatment of refractory migraine with either CGRP inhibitors or Botulinum toxin extracranial muscle injections, and with at least 1 urinary storage-phase symptom in the past month.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CGRP inhibitor; Ubrogepant (Ubrelvy™); Rimegepant (Nurtec®); Atogepant (Qulipta™); Eptinezumab (Vyepti®); Fremanezumab (Ajovy®); Galcanezumab (Emgality®); Erenumab (Aimovig®) dosage and duration according to provider's clinical decision.	Drug: Ubrogepant; Ubrogepant (Ubrelvy™), oral, dosage at discretion of clinical provider, for treatment of migraine headaches.; Other Names: Ubrelvy; Drug: Rimegepant; Rimegepant (Nurtec®), oral, dosage at discretion of clinical provider, for treatment of migraine headaches.; Other Names: Nurtec; Drug: Atogepant; Atogepant (Qulipta™), oral, dosage at discretion of clinical provider, for treatment of migraine headaches.; Other Names: Qulipta; Drug: Eptinezumab; Eptinezumab (Vyepti®) injection, dosage at discretion of clinical provider, for treatment of migraine headaches.; Other Names: Vyepti; Drug: Fremanezumab; Fremanezumab (Ajovy®) injection, dosage at discretion of clinical provider, for treatment of migraine headaches.; Other Names: Ajovy; Drug: Galcanezumab; Galcanezumab (Emgality®) injection, dosage at discretion of clinical provider, for treatment of migraine headaches.; Other Names: Emgality; Drug: Erenumab; Erenumab (Aimovig®) injection, dosage at discretion of clinical provider, for treatment of migraine headaches.; Other Names: Aimovig
BoNTA extracranial muscle injections; Botolinum toxin A (Botox) Injection into extracranial muscles to treat migraine. Dosage and duration according to provider's clinical decision	Drug: Botulinum toxin A; Botolinum toxin A (Botox) injections into extracranial muscles, dosage at discretion of clinical provider, for treatment of migraines.; Other Names: Botox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in OAB symptoms	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.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in bladder pain symptoms	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.	3 months
rates of LUTS and LUTS-related quality of life (QoL) in patients with chronic refractory migraine.	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.	3 months

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Howard B Goldman, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Actual): January 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Disease; Headache Disorders, Primary; Headache Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder, Overactive; Syndrome; Cystitis; Migraine Disorders; Cystitis, Interstitial; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Analgesics; Sensory System Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Calcitonin Gene-Related Peptide Receptor Antagonists; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Erenumab
• Other Study ID Numbers: 23-1101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: no plan to share with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No