Neurophysiological, Biomolecular and Psychological Aspects of Erenumab Treatment in Chronic Migraine

NCT04361721 | Unknown FDA Drug

• 1 other identifier: EreCM2019
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Monoclonal antibodies (mABs) targeting calcitonin gene-related peptide (CGRP) proved effective in the preventive treatment of episodic and chronic migraine as well as in difficult-to-treat patients such as those who had previously failed multiple prevention treatments or those with associated medication overuse (MO). A characteristic dysfunction in Chronic Migraine (CM) is sensitization, occurring peripherally in the trigeminovascular system but then spreading to the central nervous system, where it manifests with an increased neuronal excitability in multiple areas. Several neurophysiological studies in CM patients have demonstrated the occurrence of central sensitization in the brain as well as at the spinal level. MicroRNAs (miRNAs) are involved in the generation and maintenance of chronic pain. Current evidence suggests that specific miRNAs may also play a role in migraine, thus representing possible biomarkers of the disease. A previous study reported an upregulation of miR-34a-5p and miR-382-5p, implicated in the regulation of GABAergic signaling and IL-10 gene expression respectively, during migraine attacks. The aim of this open label, hypothesis generating study is the evaluation of the impact of erenumab treatment on neurophysiological, biomolecular and psychological aspects in a representative cohort of CM patients who had previously failed at least 2 preventive treatments.

Conditions

Chronic Migraine

Keywords

Spinal sensitization; Biomarkers; Anti CGRP monoclonal antibodies; Migraine phenotypes

Outcome Measures

Primary Outcomes (1)

• Spinal sensitization

  Measured by the temporal summation threshold (TST) of the nociceptive withdrawal reflex

  Change in TST (mA) at T3 (12 weeks later) when compared to baseline (T0)

Secondary Outcomes (13)

• Spinal sensitization

  Change in RTh (mA) at T3 (12 weeks later) when compared to baseline (T0)

• Inflammatory biomarker profile

  Change in miR-382-5p at T3 (12 weeks later) when compared to baseline (T0)

• inflammatory biomarker profile

  Change in miR-34a-5p at T3 (12 weeks later) when compared to baseline (T0)

• Migraine Disability Assessment (MIDAS)

  Change in MIDAS score at T3 (12 weeks later) when compared to baseline (T0)

• Headache Impact Test-6 (HIT-6)

  Change in HIT-6 score at T3 (12 weeks later) when compared to baseline (T0)

Study Arms (1)

Chronic migraine patients

Three monthly administration of erenumab 70 mg subcutaneously.

Drug: Erenumab

Interventions

Erenumab DRUG

First injection of erenumab 70 mg subcutaneously was administered in hospital. The second injection of erenumab 70 mg was administered in hospital after 28 days, while the third and last dose of erenumab 70 mg was self-administered at home by the patients themselves after an additional 28-day interval.

Chronic migraine patients

Eligibility Criteria

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

Study Population

Forty patients, affected by CM or CM+MO according to the International Classification of Headache Disorders (ICHD) -3 criteria were enrolled.

You may qualify if:

• age 18 to 65 years
• history of CM or CM+MO for at least 12 months prior to enrollment \[10\]
• previous failure of at least two different pharmacological classes of preventive therapies

You may not qualify if:

• other neurologic or neuropsychiatric diseases
• other chronic painful syndromes
• other types of primary or secondary headaches
• use of more than one preventive medication at baseline
• previous reported adverse reaction to latex
• pregnancy or lactation

Sponsors & Collaborators

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

Study Sites (1)

IRCCS Mondino Foundation

Pavia, 27100, Italy

RECRUITING

Related Publications (22)

• Charles A, Pozo-Rosich P. Targeting calcitonin gene-related peptide: a new era in migraine therapy. Lancet. 2019 Nov 9;394(10210):1765-1774. doi: 10.1016/S0140-6736(19)32504-8. Epub 2019 Oct 23.

  PMID: 31668411 BACKGROUND

• Ashina M, Tepper S, Brandes JL, Reuter U, Boudreau G, Dolezil D, Cheng S, Zhang F, Lenz R, Klatt J, Mikol DD. Efficacy and safety of erenumab (AMG334) in chronic migraine patients with prior preventive treatment failure: A subgroup analysis of a randomized, double-blind, placebo-controlled study. Cephalalgia. 2018 Sep;38(10):1611-1621. doi: 10.1177/0333102418788347. Epub 2018 Jul 8.

  PMID: 29984601 BACKGROUND

• Tepper SJ, Diener HC, Ashina M, Brandes JL, Friedman DI, Reuter U, Cheng S, Nilsen J, Leonardi DK, Lenz RA, Mikol DD. Erenumab in chronic migraine with medication overuse: Subgroup analysis of a randomized trial. Neurology. 2019 May 14;92(20):e2309-e2320. doi: 10.1212/WNL.0000000000007497. Epub 2019 Apr 17.

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• De Icco R, Perrotta A, Grillo V, Cosentino G, Sances G, Sandrini G, Tassorelli C. Experimentally induced spinal nociceptive sensitization increases with migraine frequency: a single-blind controlled study. Pain. 2020 Feb;161(2):429-438. doi: 10.1097/j.pain.0000000000001726.

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• Bottiroli S, De Icco R, Vaghi G, Pazzi S, Guaschino E, Allena M, Ghiotto N, Martinelli D, Tassorelli C, Sances G. Psychological predictors of negative treatment outcome with Erenumab in chronic migraine: data from an open label long-term prospective study. J Headache Pain. 2021 Oct 2;22(1):114. doi: 10.1186/s10194-021-01333-4.

  PMID: 34600468 DERIVED

• De Icco R, Fiamingo G, Greco R, Bottiroli S, Demartini C, Zanaboni AM, Allena M, Guaschino E, Martinelli D, Putorti A, Grillo V, Sances G, Tassorelli C. Neurophysiological and biomolecular effects of erenumab in chronic migraine: An open label study. Cephalalgia. 2020 Oct;40(12):1336-1345. doi: 10.1177/0333102420942230. Epub 2020 Jul 26.

  PMID: 32715736 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

RNA concentration was determined by absorbance at 230 and 280 nm using the NanoDrop Spectrophotometer (Euroclone Milano). Synthesis of cDNA was performed by using MirXMirna First strand Synthesis (Takara-Diatech, Jesi-An Italy) and TB Green q-Rt PCR is used (Takara-Diatech, Jesi-An Italy) to determine expression levels of miRNA-34a-5p and miRNA-382-5p. The denaturation was performed at 95°C and the amplification was performed through two-step cycling (95-60°C) for 40 cycles with a Light Cycler 480 Instrument RT-PCR Detection System (Roche, Milan, Italy). Target gene expression levels was normalized with U6 (a type of small nuclear RNA), used as housekeeping gene. Gene expression levels were calculated according to 2-∆Ct = 2 - (Ct gene - Ct housekeeping gene) formula by using Ct values.

MeSH Terms

Interventions

erenumab

Study Officials

• Cristina Tassorelli, MD

  IRCCS Mondino Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roberto De Icco, MD

CONTACT

0039 382 380425; roberto.deicco@mondino.it

Cinzia Fattore, MD

CONTACT

0039 382 380385; cinzia.fattore@mondino.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: April 24, 2020
• Study Start: January 15, 2020
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2021
• Last Updated: April 19, 2021

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)