MR-Spectroscopy: Investigating neurochemical changes in brain metabolism in migraineurs before and after CGRP-Antibody treatment – a randomized, controlled, open-label trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medizinische Universitaet Innsbruck

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

21 Feb 2022 → 20 Oct 2025

Decision date (initial)

2024-10-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517079-19-00

EudraCT number

2021-006219-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To investigate whether CGRP-antibody treatment (Fremanezumab 225mg monthly) leads to neurochemical changes in the occipital cortex and the thalamus of patients with migraine with and without aura.

Secondary objectives 1

1. Identification of possible correlations between disease severity, headache frequency an measured metabolic markers

Conditions and MedDRA coding

migraine

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Written informed consent must be obtained before assessment is performed
2. Adults > 18 and < 65 of age upon entry into screening
3. Documented history of migraine with or without aura > 12 months prior to screening according to the International Classification of Headache Disorders - 3rd Edition (ICHD-3)
4. Migraine frequency ≥ 4 and ≤ 15 migraine days per month across the 3 months prior to screening based on retrospective reporting
5. Subject has not received a CGRP mAB for migraine prophylaxis in the past
6. Subject can differentiate migraine from other headaches
7. Lack of contraindication for MRI

Exclusion criteria 21

1. Older than 50 years of age at migraine onset
2. Human immunodeficiency virus (HIV) infection by history
3. History or evidence of any other unstable or clinically significant medical condition
4. Subject has any clinically significant vital sign during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation
5. Coronary artery disease, myocardial infarction, stroke, transient ischemic attack, stable or unstable angina pectoris, carotid or vertebro-basilar artery disease, other cerebrovascular conditions (e.g.: AV malformation, aneurysm)
6. Evidence of drug or alcohol abuse or dependence in the past, based on medical records, patient self-report
7. Pregnant or nursing (lactating) women
8. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing with study treatment
9. Use of other investigational drugs within 5 half-lives of enrollment, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer
10. History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes
11. Previous exposure to Fremanezumab 225mg monthly or 675mg quarterly or exposure to any other prophylactic CGRP-targeted therapy (prior to and during the study)
12. History of cluster headache or hemiplegic migraine headache
13. Unable to differentiate migraine from other headaches
14. Exposure to botulinum toxin in the head and/or neck region within 4 months prior to the start of the baseline period, during the baseline period, or treatment period
15. Traditional medications and/or procedures are not allowed if not used at a stable dose/frequency for at least 3 months prior to randomization and during the study
16. Active chronic pain syndromes (e.g., fibromyalgia, chronic pelvic pain)
17. History of major psychiatric disorders (such as schizophrenia or bipolar disorder) or current evidence of depression
18. History of seizure disorder or other significant neurological conditions other than migraine
19. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years
20. Unlikely to be able to complete all protocol required study procedures to the best of the subject’s and investigator’s knowledge
21. Taken the following for any indication during 2 months prior to screening: -Ergotamines or triptans on ≥10 days per month, or -NSAIDs, acetaminophen on ≥15 days per month, or -Opioid-containing analgesics on ≥4 days per month

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in neurotransmitter level in the occipital cortex before and after 12 weeks of CGRP antibody treatment in the interventional group compared to the control group assessed by MR spectroscopy at baseline and FU visit 3.

Secondary endpoints 3

1. Comparison of neurochemical/metabolic changes between study participants with migraine with and without aura.
2. Change in migraine frequency and intensity over the treatment period assessed by MIDAS and HIT 6 questionnaire
3. Correlation between the neurochemical changes and the clinical symptoms (e.g. migraine frequency, intensity or duration)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medizinische Universitaet Innsbruck

Sponsor organisation

Medizinische Universitaet Innsbruck

Address

Innrain 52

City

Innsbruck

Postcode

6020

Country

Austria

Scientific contact point

Organisation

Medizinische Universitaet Innsbruck

Contact name

University Hospital for Neurology

Public contact point

Organisation

Medizinische Universitaet Innsbruck

Contact name

University Hospital for Neurology

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications