Status Migrainosus - Differentiating Between Responders and Non-responders

Status Migrainosus - Differentiating Between Responders and Non-responders in the Setup of Real-life Clinical Practice

The main goal of this study is to determine whether it is possible - in the setup of routine clinical care - to identify in individual patients who are clear responders to drug X, common denominators that are absent in individual patients who are non-responders to the same drug, and vice versa. All currently available knowledge about migraine pathophysiology will be utilized, using as much time as is needed to ask as many questions as are necessary, in an attempt to profile clear responders and clear non-responders.

Study Overview

• Status: Unknown
• Conditions: Migraine
• Intervention / Treatment: Drug: Bupivacaine; Drug: Naratriptan Pill; Drug: Dexamethasone; Drug: Ketorolac

Detailed Description

Recently, there has been a major focus on "evidence-based" treatments. Who could possibly argue against basing decisions on data? Since the highest level of evidence is derived from randomized double-blind controlled therapeutic trials that consider treatments rendered to large groups of patients with general diagnoses (e.g., migraine) or from a systematic review of several randomized controlled trials (meta analysis), physicians have always prided themselves on applying some type of evidence in order to select treatment. One does not want to imagine medical treatment that is purely subjective. The question, however, is how well does the evidence from trials applies to the care of individual patients? The main problem with such FDA-guided therapeutic trials is the issue of numbers vs specificity. For results to be statistically and biologically valid and important, they must include hundreds and often thousands of participants. To achieve numbers, a lumping strategy predominates over splitting. The more a trial lumps together diverse subgroups, the less specific are the results for individual patients. Given that trials have extensive inclusion and exclusion criteria, often 5 to 10 patients are screened for each patient finally enrolled in the study. Patients who are too ill, too old, too young, female and of childbearing age, incapable of giving informed consent, too complex, or too full of coexisting illnesses are often excluded from trials. Yet, these are the patients who frequently visit the headache center and to whom individualized medicine can provide the most appropriate answers.

Trials that study migraine prevention measure pain intensity and duration, attack frequency, functional disability, quality of life, number of working days lost, nausea, vomiting, and hypersensitivity to light and noise. Whether these measures are those most representative of the important aspects of a condition is an important consideration since not all end points are comparable. Some patients make their living talking. How can their aphasia (difficulty finding the right words) be compared to sensitivity to light or facial numbness? For some patients, it is the sharp pain that continuously pierces through their eyes that makes the headache impossible to tolerate whereas for others it is the ongoing nausea that prevents them from the pleasure of enjoying food, or perhaps the extreme photophobia that makes reading or working on a computer impossible and forces them to quit their jobs and seek the comfort of darkness. How is it, then, that identical weights are assigned to various patients? Physicians are not compelled to treat all patients with a given condition according to identical guidelines, as is the case in therapeutic trials that follow strict protocols. Randomized trials mandate that many patients with a general condition must be given treatment A, and the results are then compared with those of patients given treatment B or C, or placebo. Physicians, however, while caring for one patient at a time must consider several variables, including:

(1) the patient's medical problem; (2) the patient's disease risks; (3) the background, genetics, socioeconomic milieu, psychology, responsibilities, goals, and other characteristics of the patient; and (4) the benefits and risks of potential therapeutic strategies to treat the patient's conditions and to prevent conditions that he or she is at risk of developing.

An inescapable conclusion is therefore that the results of FDA-approved clinical trials fall short of allowing us to 'tailor' the right treatment to the right patient as it does not allow us to predict whether the patient we treat today will or will not benefit from an approved treatment. This conclusion questions the do-ability of translating the often stated goal of individualizing medicine from words to deeds.

Accordingly, the main goal of this proposal is determine whether it is possible - in the setup of routine clinical care - to identify in individual patients who are clear responders to drug X, common denominators that are absent in individual patients who are non-responders to the same drug, and vice versa. All currently available knowledge about migraine pathophysiology will be utilized, using as much time as is needed to ask as many questions as are necessary, in an attempt to profile clear responders and clear non-responders.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Raymond Rich-Fiondella; Phone Number: 860-231-0718; Email: Raymond.Rich-Fiondella@hhchealth.org

Study Locations

• United States
  • Connecticut
    • Wethersfield, Connecticut, United States, 06109
      • Recruiting
      • Hartford HealthCare Headache Center
      • Contact: Brooke Pellegrino, PhD; Phone Number: 860-696-2925; Email: Brooke.Pellegrino@hhchealth.org
      • Principal Investigator: Brian Grosberg, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• males and females
• ≥18 years old with no upper age limit
• patients with status migrainosus - defined as a severe migraine headache without aura lasting longer than 72 hours and considered primarily as a complication of migraine
• patients who are willing and able to provide written, informed consent

Exclusion Criteria:

• <18 years old
• unable or unwilling to provide written, informed consent
• females who are pregnant, breastfeeding, or who are trying to become pregnant
• patients who do not speak English
• any medical condition or other reason that in the opinion of the investigators makes the patient unfit or at risk to participate in the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: bupivacaine (Exparel); subjects assigned by clinician's judgment - standard care choice A	Drug: Bupivacaine; Nerve blocks with bupivacaine will be performed at initial visit; Other Names: Exparel
Active Comparator: naratriptan pill (Amerge); subjects assigned by clinician's judgment - standard care choice B	Drug: Naratriptan Pill; one pill will be administered twice each day for 5 days; Other Names: Amerge
Active Comparator: dexamethasone tablet (Decadron); subjects assigned by clinician's judgment - standard care choice C	Drug: Dexamethasone; one tablet will be administered twice each day for 3 days; Other Names: Decadron
Active Comparator: ketorolac (Toradol); subjects assigned by clinician's judgment - standard care choice D	Drug: Ketorolac; ketorolac will be administered intramuscularly (IM) or intravenously (IV) at initial visit; Other Names: Toradol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to headache relief	time to headache relief	first week

Collaborators and Investigators

• Sponsor: Hartford HealthCare
• Investigators: Principal Investigator: Brian Grosberg, MD, Physician

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2016
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): June 30, 2020

Study Registration Dates

• First Submitted: February 21, 2017
• First Submitted That Met QC Criteria: February 23, 2017
• First Posted (Actual): February 28, 2017

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 29, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: treatment; migraine; non-responder; responder
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Anesthetics, Local; Vasoconstrictor Agents; Dexamethasone; Ketorolac; Bupivacaine; Naratriptan
• Other Study ID Numbers: HHC-2016-0221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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