Efficacy of OnabotulinumtoxinA in Migraine

NCT04578782 | Completed Phase 2

• 1 other identifier: FM-BOEM
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Population studies estimate that patients who have episodic migraine transition to chronic migraine at a rate of about 2.5% per year. CM is a devastating disorder associated to severe disability. Patients with CM frequently overuse symptomatic medications in the attempt to control their disease, which adds up to the high costs associated to the disorder In this frame, it seems of the outmost importance to strive at preventing the transition from EM to CM. At the moment Onabotulinum toxin A (BoNT-A) represents the only drug specifically approved for CM prophylaxis. The aim of the present study was to evaluate the efficacy of BoNT-A in reducing the number of migraine days in a population of migraineurs with a high frequency of migraine attacks over a 12-month period.

Conditions

Migraine

Keywords

Migraine; OnabotulinumtoxinA

Outcome Measures

Primary Outcomes (1)

• Migraine days/month

  To evaluate the efficacy of BoNT-A in reducing the number of migraine days in a population of migraineurs with a high frequency of migraine attacks over a 12-month period. Based on the response in terms of percent reduction of migraine days from baseline, the following classes will be identified: * non-responders: reduction \< 30%; * partial responders: reduction ranging from 30 to 49%; * responders: reduction ranging from 50% to 74%; * optimal responders: reduction \>75%.

  In the last 16 weeks of the study period as compared to the 4 baseline weeks.

Secondary Outcomes (6)

• Monthly headache days

  In the last 16 weeks of the study period as compared to the 4 baseline weeks.

• Migraine attack intensity

  In the last 16 weeks of the study period as compared to the 4 baseline weeks.

• Monthly use of acute drugs

  In the last 16 weeks of the study period as compared to the 4 baseline weeks.

• Migraine Disability Assessment Score Questionnaire (MIDAS)

  In the last 16 weeks of the study period as compared to the 4 baseline weeks.

• Mental Status Questionnaire (MSQ)

  In the last 16 weeks of the study period as compared to the 4 baseline weeks.

Study Arms (1)

BOTOX

EXPERIMENTAL

155 UI of Botox were injected according to the approved PREEMPT protocol (the only FDA-approved injection pattern for chronic migraine), in 31 sites. From visit 5, the PREEMPT 'follow-the-pain' paradigm was applied in patients falling in the 'non-responder' or 'partial responder' classes after the first BoNT-A injection, with the possibility to increase the doses up to 195 UI in maximum 39 sites. The injections were every 3 months for 4 cycles

Drug: OnabotulinumtoxinA

Interventions

OnabotulinumtoxinA DRUG

BOTOX contains onabotulinumtoxinA, an acetylcholine release inhibitor and a neuromuscular blocking agent available in the lyophilized form of purified clostridium botulinum toxin type A, suitable for injection, for intramuscular, intradetrusor, or intradermal use. The recommended dilution is 100 Units/2 mL, with a final concentration of 5 Units per 0.1 mL. The recommended dose for treating chronic migraine is 155 Units administered intramuscularly using a sterile 30-gauge, needle as 0.1 mL (5 Units) injections per each site.

Also known as: BonT-A (Botox®)

BOTOX

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects fulfilling the diagnostic criteria for migraine without or with aura of the International Headache Classification with a number of migraine days ranging from 9 to 14 days/month in the previous 3 months.
• The frequency needs to be confirmed over the 28 days before the screening visit .
• Subjects have to be in general good health, as confirmed by medical history, baseline physical examination, baseline neurological exam and vital signs.
• Females have to be postmenopausal for at least one year, surgically sterile or otherwise incapable of pregnancy, or using an acceptable method of birth control.

You may not qualify if:

• Previous failure of more than two adequate trials of medications from different drug classes used for migraine prophylaxis;
• Onset of migraine after age 50;
• Exclusively migraine aura without headache;
• Diagnosis of other primary or secondary headache disorders. Episodic tension-tyep headache is allowed if the patient can distinguish clearly between attack of migraine and of tension-type headache;
• Another chronic painful condition (e.g. osteoarthritis, low back pain);
• A significant medical history or medical condition of neurological, cardiovascular hepatic or renal disease;
• History of suicide attempt or suicidal ideation or of a major psychiatric disorder;
• History of drug or alcohol abuse within the past two years.
• Known hypersensitivity to botulinum toxin type A or to any of the other ingredients used to form 'Botox®'
• Withdrawal criteria
• Severe side effects, diary completion insufficient for evaluation.

Sponsors & Collaborators

• IRCCS National Neurological Institute "C. Mondino" Foundation: lead

Study Sites (1)

Headache Science Center

Pavia, 27100, Italy

Location

Related Publications (9)

• Bigal ME, Serrano D, Buse D, Scher A, Stewart WF, Lipton RB. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache. 2008 Sep;48(8):1157-68. doi: 10.1111/j.1526-4610.2008.01217.x.

  PMID: 18808500 BACKGROUND

• Katsarava Z, Schneeweiss S, Kurth T, Kroener U, Fritsche G, Eikermann A, Diener HC, Limmroth V. Incidence and predictors for chronicity of headache in patients with episodic migraine. Neurology. 2004 Mar 9;62(5):788-90. doi: 10.1212/01.wnl.0000113747.18760.d2.

  PMID: 15007133 BACKGROUND

• Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ, Lipton RB. Chronic migraine is an earlier stage of transformed migraine in adults. Neurology. 2005 Nov 22;65(10):1556-61. doi: 10.1212/01.wnl.0000184477.11569.17.

  PMID: 16301481 BACKGROUND

• Lai TH, Protsenko E, Cheng YC, Loggia ML, Coppola G, Chen WT. Neural Plasticity in Common Forms of Chronic Headaches. Neural Plast. 2015;2015:205985. doi: 10.1155/2015/205985. Epub 2015 Aug 20.

  PMID: 26366304 BACKGROUND

• Perrotta A, Arce-Leal N, Tassorelli C, Gasperi V, Sances G, Blandini F, Serrao M, Bolla M, Pierelli F, Nappi G, Maccarrone M, Sandrini G. Acute reduction of anandamide-hydrolase (FAAH) activity is coupled with a reduction of nociceptive pathways facilitation in medication-overuse headache subjects after withdrawal treatment. Headache. 2012 Oct;52(9):1350-61. doi: 10.1111/j.1526-4610.2012.02170.x. Epub 2012 Jun 1.

  PMID: 22670561 BACKGROUND

• Munksgaard SB, Bendtsen L, Jensen RH. Modulation of central sensitisation by detoxification in MOH: results of a 12-month detoxification study. Cephalalgia. 2013 May;33(7):444-53. doi: 10.1177/0333102412475235. Epub 2013 Feb 21.

  PMID: 23431023 BACKGROUND

• Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB, Diener HC, Brin MF; PREEMPT 1 Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010 Jul;30(7):793-803. doi: 10.1177/0333102410364676. Epub 2010 Mar 17.

  PMID: 20647170 BACKGROUND

• Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, Silberstein SD, Brin MF; PREEMPT 2 Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010 Jul;30(7):804-14. doi: 10.1177/0333102410364677. Epub 2010 Mar 17.

  PMID: 20647171 BACKGROUND

• Martinelli D, Arceri S, De Icco R, Allena M, Guaschino E, Ghiotto N, Bitetto V, Castellazzi G, Cosentino G, Sances G, Tassorelli C. BoNT-A efficacy in high frequency migraine: an open label, single arm, exploratory study applying the PREEMPT paradigm. Cephalalgia. 2022 Feb;42(2):170-175. doi: 10.1177/03331024211034508. Epub 2021 Aug 18.

  PMID: 34404257 DERIVED

MeSH Terms

Conditions

Migraine Disorders

Interventions

Botulinum Toxins, Type A; incobotulinumtoxinA

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Cristina Tassorelli, MD

  Headache Science Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 8, 2020
• Study Start: March 13, 2018
• Primary Completion: May 31, 2020
• Study Completion: May 31, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-09

Locations

IT (1)