The FreMRI Study: Advanced MRI on Migraine Patients Treated With Fremanezumab

NCT06244823 | Unknown Phase 4

• 2 other identifiers: CASVE 20-4692020-004509-30
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this open-label, single-blind, controlled-trial is to evaluate brain changes evaluated with diffusion Magnetic Resonance Imaging (MRI) and functional MRI in patients with high-frequency episodic migraine and chronic migraine that will be treated with Fremanezumab, 12 weeks after the treatment onset, compared with the baseline. Type of study: Phase IV clinical trial Participant population: high-frequency episodic migraine and chronic migraine. Participants will be treated with Fremanezumab.

Conditions

Migraine Disorders; Migraine With Aura; Migraine Without Aura; Brain Diseases

Keywords

Treatment outcomes; Preventive treatment; Brain functional changes; Brain structural changes

Outcome Measures

Primary Outcomes (12)

• Morphometric MRI parameters change from baseline during the 12-week period after the administration of Fremanezumab 1

  Cortical curvature

  Baseline, week 12-15

• Morphometric MRI parameters change from baseline during the 12-week period after the administration of Fremanezumab 2.

  Cortical thickness

  Baseline, week 12-15

• Morphometric MRI parameters change from baseline during the 12-week period after the administration of Fremanezumab 3.

  Gray matter volume

  Baseline, week 12-15

• Morphometric MRI parameters change from baseline during the 12-week period after the administration of Fremanezumab 4.

  Surface area,

  Baseline, week 12-15

• Diffusion MRI descriptors change from baseline during the 12-week period after the administration of Fremanezumab 1.

  Fractional anisotropy

  Baseline, week 12-15

• Diffusion MRI descriptors change from baseline during the 12-week period after the administration of Fremanezumab 2.

  Mean diffusivity

  Baseline, week 12-15

• Diffusion MRI descriptors change from baseline during the 12-week period after the administration of Fremanezumab 3.

  Radial diffusivity

  Baseline, week 12-15

• Diffusion MRI descriptors change from baseline during the 12-week period after the administration of Fremanezumab 4.

  Axial diffusivity

  Baseline, week 12-15

• Structural connectivity change from baseline during the 12-week period after the administration of Fremanezumab 1.

  Number of streamlines in the connection between two regions

  Baseline, week 12-15

• Structural connectivity change from baseline during the 12-week period after the administration of Fremanezumab 2.

  Mean fractional anisotropy in the connection between two regions

  Baseline, week 12-15

• Structural connectivity change from baseline during the 12-week period after the administration of Fremanezumab 3.

  Mean axial diffusivity in the connection between two regions

  Baseline, week 12-15

• Resting-state functional connectivity change from baseline during the 12-week period after the administration of Fremanezumab.

  Z-score

  Baseline, week 12-15

Secondary Outcomes (22)

• Relationship between morphometric MRI parameters and the change in monthly migraine days 1.

  Baseline, week 12-15

• Relationship between morphometric MRI parameters and the change in monthly migraine days 2.

  Baseline, week 12-15

• Relationship between morphometric MRI parameters and the change in monthly migraine days 3.

  Baseline, week 12-15

• Relationship between morphometric MRI parameters and the change in monthly migraine days 4.

  Baseline, week 12-15

• Relationship between diffusion descriptors and the change in monthly migraine days 1.

  Baseline, week 12-15

Other Outcomes (5)

• Relationship between morphometric MRI parameters and the change in monthly intense headache days 1.

  Baseline, week 12-15

• Relationship between morphometric MRI parameters and the change in monthly intense headache days 2.

  Baseline, week 12-15

• Relationship between morphometric MRI parameters and the change in monthly intense headache days 3.

  Baseline, week 12-15

Study Arms (1)

Fremanezumab

EXPERIMENTAL

Patients will be treated with 225 mg of subcutaneous injections of Fremanezumab per month. Patients will do four monthly additional hospital visits. During each visit, occurrence of any adverse event will be interrogated; clinical situation will be analyzed and Fremanezumab will be administered. Visits will be performed at weeks 0, 4 and 8. Last visit will be performed after 12 weeks, without Fremanezumab injection.

Drug: Fremanezumab Prefilled Syringe

Interventions

Fremanezumab Prefilled Syringe DRUG

MRI will be scanned prior to the first administration of Fremanezumab, within 0-14 days, prior to Fremanezumab injection. The second MRI will be acquired at 12 ± 1 weeks after the first Fremanezumab injection.Images will be acquired during interictal periods, defined as at least 24 hours from last migraine attack. All the scans will be acquired during the same session, starting with the T1-weighted scan, followed by the diffusion-weighted scan and ending with the rs-fMRI scan. Total acquisition time for a single subject is approximately 28 minutes, divided in the following periods of time: six minutes for the T1-weighted scan, 12 minutes for the diffusion-weighted scan and 10 minutes for the rs-fMRI scan. If we consider patient preparation, obtainment of documents and informed consent form, the whole process will take about 50-70 minutes.

Fremanezumab

Eligibility Criteria

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

You may qualify if:

• Definite diagnosis of Migraine With Aura or Migraine Without Aura according to the International Classification of Headache Disorders, 3rd version (IHCD-3) (1).
• Age between 18 and 65 years old.
• Providing signed informed consent form.
• Diagnosis of migraine before 50 years old.
• History of migraine during at least 12 months prior to the study.
• With eight or more migraine days per month within the last three months

You may not qualify if:

• Presence of other primary headache disorders other than infrequent tension-type headache or medication overuse headache (MOH).
• Participation of MOH patients will be restricted to a maximum of 50% of the total sample.
• Prior use of Fremanezumab or another monoclonal antibody targeting CGRP or CGRP receptor.
• Prior use of less than two or more than four preventive drugs according to the local national guidelines (34), with inadequate response after sufficient doses and enough time or lack of tolerability.
• Any medical condition that might prevent study completion or interfere with interpretation of results.
• History of any neurological or neurosurgical condition affecting the brain.
• History of moderate-severe head trauma.
• History of other chronic pain syndrome with a frequency of five or more days of pain per month.
• Presence of daily headache
• Pregnant or breastfeeding women.
• Current or recent use of any other prophylactic treatment in the preceding five half-lives prior to the start.
• Exposure to onabotulinumtoxinA in the preceding four months.
• Any expected surgery during the study.
• Use of opioids or barbiturates.
• Any condition contraindicating an MRI acquisition.

Sponsors & Collaborators

• Hospital Clínico Universitario de Valladolid: lead
• University of Valladolid: collaborator
• Complejo Asistencial Universitario de Palencia: collaborator
• Complejo Público Asistencial de Zamora: collaborator

Study Sites (1)

Hospital Clínico Universitario de Valladolid

Valladolid, 47010, Spain

RECRUITING

Related Publications (67)

• Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.

  PMID: 29368949 BACKGROUND

• Karsan N, Bose P, Goadsby PJ. The Migraine Premonitory Phase. Continuum (Minneap Minn). 2018 Aug;24(4, Headache):996-1008. doi: 10.1212/CON.0000000000000624.

  PMID: 30074545 BACKGROUND

• Quintela E, Castillo J, Munoz P, Pascual J. Premonitory and resolution symptoms in migraine: a prospective study in 100 unselected patients. Cephalalgia. 2006 Sep;26(9):1051-60. doi: 10.1111/j.1468-2982.2006.01157.x.

  PMID: 16919055 BACKGROUND

• Giffin NJ, Ruggiero L, Lipton RB, Silberstein SD, Tvedskov JF, Olesen J, Altman J, Goadsby PJ, Macrae A. Premonitory symptoms in migraine: an electronic diary study. Neurology. 2003 Mar 25;60(6):935-40. doi: 10.1212/01.wnl.0000052998.58526.a9.

  PMID: 12654956 BACKGROUND

• Afridi KS, Kaube H, Goadsby JP. Glyceryl trinitrate triggers premonitory symptoms in migraineurs. Pain. 2004 Aug;110(3):675-680. doi: 10.1016/j.pain.2004.05.007.

  PMID: 15288408 BACKGROUND

• Guo S, Vollesen ALH, Olesen J, Ashina M. Premonitory and nonheadache symptoms induced by CGRP and PACAP38 in patients with migraine. Pain. 2016 Dec;157(12):2773-2781. doi: 10.1097/j.pain.0000000000000702.

  PMID: 27842045 BACKGROUND

• Burstein R, Jakubowski M. Unitary hypothesis for multiple triggers of the pain and strain of migraine. J Comp Neurol. 2005 Dec 5;493(1):9-14. doi: 10.1002/cne.20688.

  PMID: 16258903 BACKGROUND

• Noseda R, Kainz V, Borsook D, Burstein R. Neurochemical pathways that converge on thalamic trigeminovascular neurons: potential substrate for modulation of migraine by sleep, food intake, stress and anxiety. PLoS One. 2014 Aug 4;9(8):e103929. doi: 10.1371/journal.pone.0103929. eCollection 2014.

  PMID: 25090640 BACKGROUND

• Denuelle M, Fabre N, Payoux P, Chollet F, Geraud G. Hypothalamic activation in spontaneous migraine attacks. Headache. 2007 Nov-Dec;47(10):1418-26. doi: 10.1111/j.1526-4610.2007.00776.x.

  PMID: 18052951 BACKGROUND

• Maniyar FH, Sprenger T, Monteith T, Schankin C, Goadsby PJ. Brain activations in the premonitory phase of nitroglycerin-triggered migraine attacks. Brain. 2014 Jan;137(Pt 1):232-41. doi: 10.1093/brain/awt320. Epub 2013 Nov 25.

  PMID: 24277718 BACKGROUND

• Stankewitz A, Aderjan D, Eippert F, May A. Trigeminal nociceptive transmission in migraineurs predicts migraine attacks. J Neurosci. 2011 Feb 9;31(6):1937-43. doi: 10.1523/JNEUROSCI.4496-10.2011.

  PMID: 21307231 BACKGROUND

• Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain. 2016 Jul;139(Pt 7):1987-93. doi: 10.1093/brain/aww097. Epub 2016 May 5.

  PMID: 27190019 BACKGROUND

• Beissner F, Meissner K, Bar KJ, Napadow V. The autonomic brain: an activation likelihood estimation meta-analysis for central processing of autonomic function. J Neurosci. 2013 Jun 19;33(25):10503-11. doi: 10.1523/JNEUROSCI.1103-13.2013.

  PMID: 23785162 BACKGROUND

• Jenkinson M, Beckmann CF, Behrens TE, Woolrich MW, Smith SM. FSL. Neuroimage. 2012 Aug 15;62(2):782-90. doi: 10.1016/j.neuroimage.2011.09.015. Epub 2011 Sep 16.

  PMID: 21979382 BACKGROUND

• Jensen K, Tuxen C, Olesen J. Pericranial muscle tenderness and pressure-pain threshold in the temporal region during common migraine. Pain. 1988 Oct;35(1):65-70. doi: 10.1016/0304-3959(88)90277-1.

  PMID: 3200599 BACKGROUND

• Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa ZH. An association between migraine and cutaneous allodynia. Ann Neurol. 2000 May;47(5):614-24.

  PMID: 10805332 BACKGROUND

• Rodriguez C, Herrero-Velazquez S, Ruiz M, Baron J, Carreres A, Rodriguez-Valencia E, Guerrero AL, Madeleine P, Cuadrado ML, Fernandez-de-Las-Penas C. Pressure pain sensitivity map of multifocal nummular headache: a case report. J Headache Pain. 2015;16:523. doi: 10.1186/s10194-015-0523-7. Epub 2015 Apr 30.

  PMID: 25929432 BACKGROUND

• Fernandez-de-las-Penas C, Madeleine P, Cuadrado ML, Ge HY, Arendt-Nielsen L, Pareja JA. Pressure pain sensitivity mapping of the temporalis muscle revealed bilateral pressure hyperalgesia in patients with strictly unilateral migraine. Cephalalgia. 2009 Jun;29(6):670-6. doi: 10.1111/j.1468-2982.2008.01831.x.

  PMID: 19891059 BACKGROUND

• Dodick D, Silberstein S. Central sensitization theory of migraine: clinical implications. Headache. 2006 Nov;46 Suppl 4:S182-91. doi: 10.1111/j.1526-4610.2006.00602.x.

  PMID: 17078850 BACKGROUND

• Bigal ME, Ashina S, Burstein R, Reed ML, Buse D, Serrano D, Lipton RB; AMPP Group. Prevalence and characteristics of allodynia in headache sufferers: a population study. Neurology. 2008 Apr 22;70(17):1525-33. doi: 10.1212/01.wnl.0000310645.31020.b1.

  PMID: 18427069 BACKGROUND

• Castillo J, Munoz P, Guitera V, Pascual J. Kaplan Award 1998. Epidemiology of chronic daily headache in the general population. Headache. 1999 Mar;39(3):190-6. doi: 10.1046/j.1526-4610.1999.3903190.x.

  PMID: 15613213 BACKGROUND

• Stovner LJ, Zwart JA, Hagen K, Terwindt GM, Pascual J. Epidemiology of headache in Europe. Eur J Neurol. 2006 Apr;13(4):333-45. doi: 10.1111/j.1468-1331.2006.01184.x.

  PMID: 16643310 BACKGROUND

• 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

• Hubbard CS, Becerra L, Smith JH, DeLange JM, Smith RM, Black DF, Welker KM, Burstein R, Cutrer FM, Borsook D. Brain Changes in Responders vs. Non-Responders in Chronic Migraine: Markers of Disease Reversal. Front Hum Neurosci. 2016 Oct 6;10:497. doi: 10.3389/fnhum.2016.00497. eCollection 2016.

  PMID: 27766076 BACKGROUND

• Bigal ME, Edvinsson L, Rapoport AM, Lipton RB, Spierings EL, Diener HC, Burstein R, Loupe PS, Ma Y, Yang R, Silberstein SD. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015 Nov;14(11):1091-100. doi: 10.1016/S1474-4422(15)00245-8. Epub 2015 Sep 30.

  PMID: 26432181 BACKGROUND

• Bigal ME, Dodick DW, Rapoport AM, Silberstein SD, Ma Y, Yang R, Loupe PS, Burstein R, Newman LC, Lipton RB. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015 Nov;14(11):1081-90. doi: 10.1016/S1474-4422(15)00249-5. Epub 2015 Sep 30.

  PMID: 26432182 BACKGROUND

• Dodick DW, Silberstein SD, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E. Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial. JAMA. 2018 May 15;319(19):1999-2008. doi: 10.1001/jama.2018.4853.

  PMID: 29800211 BACKGROUND

• Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E. Fremanezumab for the Preventive Treatment of Chronic Migraine. N Engl J Med. 2017 Nov 30;377(22):2113-2122. doi: 10.1056/NEJMoa1709038.

  PMID: 29171818 BACKGROUND

• Silberstein SD, McAllister P, Ning X, Faulhaber N, Lang N, Yeung P, Schiemann J, Aycardi E, Cohen JM, Janka L, Yang R. Safety and Tolerability of Fremanezumab for the Prevention of Migraine: A Pooled Analysis of Phases 2b and 3 Clinical Trials. Headache. 2019 Jun;59(6):880-890. doi: 10.1111/head.13534. Epub 2019 Apr 12.

  PMID: 30977520 BACKGROUND

• Aoki KR. Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology. 2005 Oct;26(5):785-93. doi: 10.1016/j.neuro.2005.01.017. Epub 2005 Jul 5.

  PMID: 16002144 BACKGROUND

• Planchuelo-Gomez A, Garcia-Azorin D, Guerrero AL, Rodriguez M, Aja-Fernandez S, de Luis-Garcia R. Gray Matter Structural Alterations in Chronic and Episodic Migraine: A Morphometric Magnetic Resonance Imaging Study. Pain Med. 2020 Nov 1;21(11):2997-3011. doi: 10.1093/pm/pnaa271.

  PMID: 33040149 BACKGROUND

• Planchuelo-Gomez A, Garcia-Azorin D, Guerrero AL, Aja-Fernandez S, Rodriguez M, de Luis-Garcia R. White matter changes in chronic and episodic migraine: a diffusion tensor imaging study. J Headache Pain. 2020 Jan 2;21(1):1. doi: 10.1186/s10194-019-1071-3.

  PMID: 31898478 BACKGROUND

• Planchuelo-Gomez A, Garcia-Azorin D, Guerrero AL, Aja-Fernandez S, Rodriguez M, de Luis-Garcia R. Structural connectivity alterations in chronic and episodic migraine: A diffusion magnetic resonance imaging connectomics study. Cephalalgia. 2020 Apr;40(4):367-383. doi: 10.1177/0333102419885392. Epub 2019 Nov 1.

  PMID: 31674222 BACKGROUND

• Planchuelo-Gómez A, García-Azorín D, Guerrero AL, Aja-Fernández S, Antón-Juarrós S, de Luis García R. Development of a response prediction model for the chronic migraine treatment response by grey matter morphometry in magnetic resonance. LXXI Spanish Society of Neurology congress, Sevilla Nov 21st 2019, Spain.

  BACKGROUND

• García-Azorín D, Porta-Etessam J, Guerrero-Peral AL. Official guidelines of the Neuropharmacology study group, Spanish Society of Neurology, Start & Stop Guidelines, Ed Luzan 5, 2019

  BACKGROUND

• Krebs K, Rorden C, Androulakis XM. Resting State Functional Connectivity After Sphenopalatine Ganglion Blocks in Chronic Migraine With Medication Overuse Headache: A Pilot Longitudinal fMRI Study. Headache. 2018 May;58(5):732-743. doi: 10.1111/head.13318.

  PMID: 29878344 BACKGROUND

• Fusar-Poli P, Smieskova R, Kempton MJ, Ho BC, Andreasen NC, Borgwardt S. Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neurosci Biobehav Rev. 2013 Sep;37(8):1680-91. doi: 10.1016/j.neubiorev.2013.06.001. Epub 2013 Jun 14.

  PMID: 23769814 BACKGROUND

• Yrondi A, Peran P, Sauvaget A, Schmitt L, Arbus C. Structural-functional brain changes in depressed patients during and after electroconvulsive therapy. Acta Neuropsychiatr. 2018 Feb;30(1):17-28. doi: 10.1017/neu.2016.62. Epub 2016 Nov 23.

  PMID: 27876102 BACKGROUND

• Smith SM. Fast robust automated brain extraction. Hum Brain Mapp. 2002 Nov;17(3):143-55. doi: 10.1002/hbm.10062.

  PMID: 12391568 BACKGROUND

• Dale AM, Fischl B, Sereno MI. Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage. 1999 Feb;9(2):179-94. doi: 10.1006/nimg.1998.0395.

  PMID: 9931268 BACKGROUND

• Fischl B, Liu A, Dale AM. Automated manifold surgery: constructing geometrically accurate and topologically correct models of the human cerebral cortex. IEEE Trans Med Imaging. 2001 Jan;20(1):70-80. doi: 10.1109/42.906426.

  PMID: 11293693 BACKGROUND

• Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, van der Kouwe A, Killiany R, Kennedy D, Klaveness S, Montillo A, Makris N, Rosen B, Dale AM. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron. 2002 Jan 31;33(3):341-55. doi: 10.1016/s0896-6273(02)00569-x.

  PMID: 11832223 BACKGROUND

• Segonne F, Dale AM, Busa E, Glessner M, Salat D, Hahn HK, Fischl B. A hybrid approach to the skull stripping problem in MRI. Neuroimage. 2004 Jul;22(3):1060-75. doi: 10.1016/j.neuroimage.2004.03.032.

  PMID: 15219578 BACKGROUND

• Reuter M, Schmansky NJ, Rosas HD, Fischl B. Within-subject template estimation for unbiased longitudinal image analysis. Neuroimage. 2012 Jul 16;61(4):1402-18. doi: 10.1016/j.neuroimage.2012.02.084. Epub 2012 Mar 10.

  PMID: 22430496 BACKGROUND

• Desikan RS, Segonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, Buckner RL, Dale AM, Maguire RP, Hyman BT, Albert MS, Killiany RJ. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006 Jul 1;31(3):968-80. doi: 10.1016/j.neuroimage.2006.01.021. Epub 2006 Mar 10.

  PMID: 16530430 BACKGROUND

• Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TE. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage. 2006 Jul 15;31(4):1487-505. doi: 10.1016/j.neuroimage.2006.02.024. Epub 2006 Apr 19.

  PMID: 16624579 BACKGROUND

• Hagmann P, Jonasson L, Maeder P, Thiran JP, Wedeen VJ, Meuli R. Understanding diffusion MR imaging techniques: from scalar diffusion-weighted imaging to diffusion tensor imaging and beyond. Radiographics. 2006 Oct;26 Suppl 1:S205-23. doi: 10.1148/rg.26si065510.

  PMID: 17050517 BACKGROUND

• Fornito A, Bullmore ET. Connectomics: a new paradigm for understanding brain disease. Eur Neuropsychopharmacol. 2015 May;25(5):733-48. doi: 10.1016/j.euroneuro.2014.02.011. Epub 2014 Mar 5.

  PMID: 24726580 BACKGROUND

• Sinke MRT, Otte WM, Christiaens D, Schmitt O, Leemans A, van der Toorn A, Sarabdjitsingh RA, Joels M, Dijkhuizen RM. Diffusion MRI-based cortical connectome reconstruction: dependency on tractography procedures and neuroanatomical characteristics. Brain Struct Funct. 2018 Jun;223(5):2269-2285. doi: 10.1007/s00429-018-1628-y. Epub 2018 Feb 20.

  PMID: 29464318 BACKGROUND

• Veraart J, Novikov DS, Christiaens D, Ades-Aron B, Sijbers J, Fieremans E. Denoising of diffusion MRI using random matrix theory. Neuroimage. 2016 Nov 15;142:394-406. doi: 10.1016/j.neuroimage.2016.08.016. Epub 2016 Aug 11.

  PMID: 27523449 BACKGROUND

• Andersson JLR, Sotiropoulos SN. An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging. Neuroimage. 2016 Jan 15;125:1063-1078. doi: 10.1016/j.neuroimage.2015.10.019. Epub 2015 Oct 20.

  PMID: 26481672 BACKGROUND

• Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23 Suppl 1:S208-19. doi: 10.1016/j.neuroimage.2004.07.051.

  PMID: 15501092 BACKGROUND

• Zhang Y, Brady M, Smith S. Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging. 2001 Jan;20(1):45-57. doi: 10.1109/42.906424.

  PMID: 11293691 BACKGROUND

• Aja-Fernández S, Tristán-Vega A, Molendowska M, Pieciak T, de Luis-García R. Return-to-the-origin probability calculation in single shell acquisitions. International Society of Magnetic Resonance in Medicine 26th Annual Meeting and Exhibition. Paris, France; 2018:1414.

  BACKGROUND

• Dhollander T, Raffelt D, Connelly A. Unsupervised 3-tissue response function estimation from single-shell or multi-shell diffusion MR data without a co-registered T1 image. ISMRM Work Break Barriers Diffus MRI 2016; 5.

  BACKGROUND

• Rueckert D, Sonoda LI, Hayes C, Hill DL, Leach MO, Hawkes DJ. Nonrigid registration using free-form deformations: application to breast MR images. IEEE Trans Med Imaging. 1999 Aug;18(8):712-21. doi: 10.1109/42.796284.

  PMID: 10534053 BACKGROUND

• Wakana S, Jiang H, Nagae-Poetscher LM, van Zijl PC, Mori S. Fiber tract-based atlas of human white matter anatomy. Radiology. 2004 Jan;230(1):77-87. doi: 10.1148/radiol.2301021640. Epub 2003 Nov 26.

  PMID: 14645885 BACKGROUND

• Oishi K, Zilles K, Amunts K, Faria A, Jiang H, Li X, Akhter K, Hua K, Woods R, Toga AW, Pike GB, Rosa-Neto P, Evans A, Zhang J, Huang H, Miller MI, van Zijl PC, Mazziotta J, Mori S. Human brain white matter atlas: identification and assignment of common anatomical structures in superficial white matter. Neuroimage. 2008 Nov 15;43(3):447-57. doi: 10.1016/j.neuroimage.2008.07.009. Epub 2008 Jul 18.

  PMID: 18692144 BACKGROUND

• Smith RE, Tournier JD, Calamante F, Connelly A. Anatomically-constrained tractography: improved diffusion MRI streamlines tractography through effective use of anatomical information. Neuroimage. 2012 Sep;62(3):1924-38. doi: 10.1016/j.neuroimage.2012.06.005. Epub 2012 Jun 13.

  PMID: 22705374 BACKGROUND

• Jenkinson M, Bannister P, Brady M, Smith S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage. 2002 Oct;17(2):825-41. doi: 10.1016/s1053-8119(02)91132-8.

  PMID: 12377157 BACKGROUND

• Tournier JD, Calamante F, Connelly A. Determination of the appropriate b value and number of gradient directions for high-angular-resolution diffusion-weighted imaging. NMR Biomed. 2013 Dec;26(12):1775-86. doi: 10.1002/nbm.3017. Epub 2013 Aug 29.

  PMID: 24038308 BACKGROUND

• Tournier JD, Calamante F, Gadian DG, Connelly A. Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution. Neuroimage. 2004 Nov;23(3):1176-85. doi: 10.1016/j.neuroimage.2004.07.037.

  PMID: 15528117 BACKGROUND

• Tournier JD, Calamante F, Connelly A. Robust determination of the fibre orientation distribution in diffusion MRI: non-negativity constrained super-resolved spherical deconvolution. Neuroimage. 2007 May 1;35(4):1459-72. doi: 10.1016/j.neuroimage.2007.02.016. Epub 2007 Feb 21.

  PMID: 17379540 BACKGROUND

• Tournier J-D, Calamante F, Connelly A. Improved probabilistic streamlines tractography by 2nd order integration over fibre orientation distributions. Proc Int Soc Magn Reson Med. 2010; 1670.

  BACKGROUND

• Smith RE, Tournier JD, Calamante F, Connelly A. SIFT2: Enabling dense quantitative assessment of brain white matter connectivity using streamlines tractography. Neuroimage. 2015 Oct 1;119:338-51. doi: 10.1016/j.neuroimage.2015.06.092. Epub 2015 Jul 8.

  PMID: 26163802 BACKGROUND

• Whitfield-Gabrieli S, Nieto-Castanon A. Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect. 2012;2(3):125-41. doi: 10.1089/brain.2012.0073. Epub 2012 Jul 19.

  PMID: 22642651 BACKGROUND

• Akaike H. A new look at the statistical model identification. IEEE Trans Automat Contr 1974; 19: 716-23.

  BACKGROUND

Related Links

• Aja-Fernández S, de Luis-García R, Afzali M, Molendowska M, Pieciak T, Tristán-Vega A. Microstructure Diffusion Scalar Measures from Reduced MRI Acquisitions. bioRxiv. 2019. (accessed 2 November 2019)

MeSH Terms

Conditions

Migraine Disorders; Migraine with Aura; Migraine without Aura; Brain Diseases

Condition Hierarchy (Ancestors)

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

Study Officials

• Angel L Guerrero Peral, MD, PhD

  Sanidad de Castilla y León

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Garcia Azorin, MD, PhD

CONTACT

+34 665872228; davilink@hotmail.com

Yesica Gonzalez Osorio, MBA

CONTACT

+34 634330426; ygoinvestigacion@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: Given that the efficacy of Fremanezumab has been established in the pivotal trials and due to sample-size reasons, we chose an open-label study. However, in order to avoid biases as much as possible, we will blind clinical data to the imaging analysts. Patients, clinicians involved in the Fremanezumab administration and data analysts cannot be blind to the information.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Headache Unit, Department of Neurology, Principal Investigator

Model Details: The present study is an open-label, controlled-trial, single-blind trial analyzing brain changes measured by dMRI and fMRI in patients with high frequency episodic migraine and chronic migraine will be treated with Fremanezumab, 12 weeks after treatment.

Study Record Dates

• First Submitted: December 24, 2022
• First Posted: February 6, 2024
• Study Start: March 1, 2023
• Primary Completion: October 1, 2024
• Study Completion: January 1, 2025
• Last Updated: February 6, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Up to 5 years after the publication of the study.
• Access Criteria: Upon request to the corresponding study.

Locations

ES (1)