[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT04439552":3,"trial-entities:NCT04439552":162,"trial-summary:NCT04439552":165},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":27,"study_type":32,"primary_purpose":33,"phases":34,"enrollment_info":35,"interventions":38,"primary_outcomes":39,"secondary_outcomes":47,"sex":48,"minimum_age":49,"maximum_age":50,"healthy_volunteers":51,"eligibility_criteria":52,"std_ages":69,"locations":72,"central_contacts":87,"overall_officials":93,"references":96,"see_also_links":161},"NCT04439552","IRB-P00035185","fMRI and IVCM Cornea Microscopy of CXL in Keratoconus","Neuroplasticity of Pain Pathways and Corneal Afferent Regeneration Following Corneal Crosslinking (CXL) in Keratoconus","RECRUITING","2027-12","2025-12","2025-12-19","2021-10-04","Boston Children's Hospital","OTHER",false,"Evaluation of neuroplasticity of pain pathways and corneal afferent nerve regeneration following corneal crosslinking (CXL) in keratoconus patients using fMRI and corneal In Vivo Confocal Microscopy (IVCM).","Our long-term goal is to evaluate the transition from acute to chronic pain that sometimes occurs following CXL in keratoconus patients. This study will determine whether these changes can be structurally and functionally quantified using functional neuroimaging and in vivo corneal microscopy (IVCM), and whether they can be predicted based on predisposing biological and psychological factors. Our central hypothesis is that CXL produces acute pain through activation of trigeminal afferents, and that post-operative chronic pain outcomes are related to neuroplastic changes in trigeminal circuitry, corneal afferent regeneration, and psychological factors.",[19,20,21,22,23,24,25,26],"Pain, Postoperative","Pain, Chronic","Pain, Acute","Surgical Injury","Surgical Wound","Cornea Injury","Cornea","Keratoconus",[28,29,30,31],"fMRI","Corneal Microscopy","IVCM","Neuroimaging","OBSERVATIONAL",null,[],{"count":36,"type":37},60,"ESTIMATED",[],[40,44],{"measure":41,"description":42,"timeFrame":43},"Neural activity related to pain.","Pain-related brain activation measured with fMRI.","1 year",{"measure":45,"description":46,"timeFrame":43},"Corneal nerve morphology.","Afferent nerve fiber morphology measured with IVCM.",[],"ALL","8 Years","35 Years",true,{"inclusion":53,"exclusion":60,"raw_text":68},[54,55,56,57,58,54,59,56,57,58],"Age 8-35 years","Clinical diagnosis of keratoconus and seeking CXL treatment","English speaking ability sufficient to comprehend consent with parental assistance","MRI compatible","Ability to lie still for an MRI session (60 minutes)","No diagnosis of keratoconus",[61,62,63,64,65,66,67],"Claustrophobic","Weight \\> 285 lbs (weight limit of the MRI table)","Significant medical history, including:","Magnetic implants or metal-containing tattoos on their chest or above","Pregnancy","History of contact lens wear","Any allergic response to a numbing eyedrop in the past","Inclusion Criteria:\n\nCXL Group\n\n* Age 8-35 years\n* Clinical diagnosis of keratoconus and seeking CXL treatment\n* English speaking ability sufficient to comprehend consent with parental assistance\n* MRI compatible\n* Ability to lie still for an MRI session (60 minutes)\n\nControl Group\n\n* Age 8-35 years\n* No diagnosis of keratoconus\n* English speaking ability sufficient to comprehend consent with parental assistance\n* MRI compatible\n* Ability to lie still for an MRI session (60 minutes)\n\nExclusion Criteria (Both Groups):\n\n* Claustrophobic\n* Weight \\> 285 lbs (weight limit of the MRI table)\n* Significant medical history, including:\n\nCurrent DSM-IV-TR axis I psychiatric disorders. Chronic pain Significant head injury Seizures Brain tumor Cerebrovascular accident Neurological disease aside from migraine HIV-AIDs Prescription medication strongly implicated in causing dry eyes\n\n* Magnetic implants or metal-containing tattoos on their chest or above\n* Pregnancy\n* History of contact lens wear\n* Any allergic response to a numbing eyedrop in the past",[70,71],"CHILD","ADULT",[73],{"facility":13,"status":8,"city":74,"state":75,"zip":76,"country":77,"contacts":78,"geoPoint":84},"Boston","Massachusetts","02115","United States",[79],{"name":80,"role":81,"phone":82,"email":83},"Nicholas J Pondelis, BA","CONTACT","617-919-1895","nicholas.pondelis@childrens.harvard.edu",{"lat":85,"lon":86},42.35843,-71.05977,[88,92],{"name":89,"role":81,"phone":90,"email":91},"Eric A Moulton, OD PhD","617-919-6827","eric.moulton@childrens.harvard.edu",{"name":80,"role":81,"phone":82,"email":83},[94],{"name":89,"affiliation":13,"role":95},"PRINCIPAL_INVESTIGATOR",[97,101,104,107,110,113,116,119,122,125,128,131,134,137,140,143,146,149,152,155,158],{"pmid":98,"type":99,"citation":100},"26000205","BACKGROUND","Belmonte C, Acosta MC, Merayo-Lloves J, Gallar J. What Causes Eye Pain? Curr Ophthalmol Rep. 2015;3(2):111-121. doi: 10.1007\u002Fs40135-015-0073-9.",{"pmid":102,"type":99,"citation":103},"30234696","Borsook D, Youssef AM, Simons L, Elman I, Eccleston C. When pain gets stuck: the evolution of pain chronification and treatment resistance. Pain. 2018 Dec;159(12):2421-2436. doi: 10.1097\u002Fj.pain.0000000000001401.",{"pmid":105,"type":99,"citation":106},"27771327","Cruzat A, Qazi Y, Hamrah P. In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease. Ocul Surf. 2017 Jan;15(1):15-47. doi: 10.1016\u002Fj.jtos.2016.09.004. Epub 2016 Oct 19.",{"pmid":108,"type":99,"citation":109},"29550279","Downie LE, Naranjo Golborne C, Chen M, Ho N, Hoac C, Liyanapathirana D, Luo C, Wu RB, Chinnery HR. Recovery of the sub-basal nerve plexus and superficial nerve terminals after corneal epithelial injury in mice. Exp Eye Res. 2018 Jun;171:92-100. doi: 10.1016\u002Fj.exer.2018.03.012. Epub 2018 Mar 14.",{"pmid":111,"type":99,"citation":112},"22547128","Ghanem VC, Ghanem RC, de Oliveira R. Postoperative pain after corneal collagen cross-linking. Cornea. 2013 Jan;32(1):20-4. doi: 10.1097\u002FICO.0b013e31824d6fe3.",{"pmid":114,"type":99,"citation":115},"29490476","Hruschak V, Cochran G. Psychosocial predictors in the transition from acute to chronic pain: a systematic review. Psychol Health Med. 2018 Dec;23(10):1151-1167. doi: 10.1080\u002F13548506.2018.1446097. Epub 2018 Feb 28.",{"pmid":117,"type":99,"citation":118},"25350076","Hasenbring MI, Chehadi O, Titze C, Kreddig N. Fear and anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance. Pain Manag. 2014;4(5):363-74. doi: 10.2217\u002Fpmt.14.36.",{"pmid":120,"type":99,"citation":121},"16698416","Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016\u002FS0140-6736(06)68700-X.",{"pmid":123,"type":99,"citation":124},"3513592","Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiologic study of keratoconus. Am J Ophthalmol. 1986 Mar 15;101(3):267-73. doi: 10.1016\u002F0002-9394(86)90817-2.",{"pmid":126,"type":99,"citation":127},"25828778","Kinard KI, Smith AG, Singleton JR, Lessard MK, Katz BJ, Warner JE, Crum AV, Mifflin MD, Brennan KC, Digre KB. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye. Headache. 2015 Apr;55(4):543-9. doi: 10.1111\u002Fhead.12547. Epub 2015 Mar 31.",{"pmid":129,"type":99,"citation":130},"30503915","Larbig W, Andoh J, Huse E, Stahl-Corino D, Montoya P, Seltzer Z, Flor H. Pre- and postoperative predictors of phantom limb pain. Neurosci Lett. 2019 May 29;702:44-50. doi: 10.1016\u002Fj.neulet.2018.11.044. Epub 2018 Nov 29.",{"pmid":132,"type":99,"citation":133},"19674842","Moulton EA, Becerra L, Borsook D. An fMRI case report of photophobia: activation of the trigeminal nociceptive pathway. Pain. 2009 Oct;145(3):358-363. doi: 10.1016\u002Fj.pain.2009.07.018. Epub 2009 Aug 11.",{"pmid":135,"type":99,"citation":136},"31718074","Moulton EA, Borsook D. C-Fiber Assays in the Cornea vs. Skin. Brain Sci. 2019 Nov 12;9(11):320. doi: 10.3390\u002Fbrainsci9110320.",{"pmid":138,"type":99,"citation":139},"27723896","Rosenthal P, Borsook D, Moulton EA. Oculofacial Pain: Corneal Nerve Damage Leading to Pain Beyond the Eye. Invest Ophthalmol Vis Sci. 2016 Oct 1;57(13):5285-5287. doi: 10.1167\u002Fiovs.16-20557.",{"pmid":141,"type":99,"citation":142},"10815152","Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000 May;118(5):615-21. doi: 10.1001\u002Farchopht.118.5.615.",{"pmid":144,"type":99,"citation":145},"9787000","Simone DA, Nolano M, Johnson T, Wendelschafer-Crabb G, Kennedy WR. Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci. 1998 Nov 1;18(21):8947-59. doi: 10.1523\u002FJNEUROSCI.18-21-08947.1998.",{"pmid":147,"type":99,"citation":148},"2282506","Sjoberg J, Kanje M. The initial period of peripheral nerve regeneration and the importance of the local environment for the conditioning lesion effect. Brain Res. 1990 Oct 8;529(1-2):79-84. doi: 10.1016\u002F0006-8993(90)90812-p.",{"pmid":150,"type":99,"citation":151},"7980137","Tervo K, Latvala TM, Tervo TM. Recovery of corneal innervation following photorefractive keratoablation. Arch Ophthalmol. 1994 Nov;112(11):1466-70. doi: 10.1001\u002Farchopht.1994.01090230080025.",{"pmid":153,"type":99,"citation":154},"35211480","Pondelis NJ, Moulton EA. Supraspinal Mechanisms Underlying Ocular Pain. Front Med (Lausanne). 2022 Feb 8;8:768649. doi: 10.3389\u002Ffmed.2021.768649. eCollection 2021.",{"pmid":156,"type":99,"citation":157},"34901466","van der Valk Bouman ES, Pump H, Borsook D, Severinsky B, Wisse RP, Saeed HN, Moulton EA. Pain mechanisms and management in corneal cross-linking: a review. BMJ Open Ophthalmol. 2021 Nov 29;6(1):e000878. doi: 10.1136\u002Fbmjophth-2021-000878. eCollection 2021.",{"pmid":159,"type":99,"citation":160},"33931393","Dieckmann G, Borsook D, Moulton E. Neuropathic corneal pain and dry eye: a continuum of nociception. Br J Ophthalmol. 2022 Aug;106(8):1039-1043. doi: 10.1136\u002Fbjophthalmol-2020-318469. Epub 2021 Apr 30.",[],{"nct_id":4,"conditions":163,"biomarkers":164},[26],[],{"nct_id":4,"found":51,"summary":166,"prompt_version":176},{"design":167,"status":168,"heading":169,"summary":170,"follow_up":171,"word_count":172,"commitments":173,"compensation":174,"drugs_mentioned":175},"This is an observational study planning to enroll 60 participants, divided into a CXL group and a control group.","completed","Observational Study of CXL in Keratoconus and Pain","This observational study is looking at how corneal crosslinking (CXL) treatment for keratoconus affects pain. Researchers want to understand if changes in pain can be measured in the brain using fMRI (functional magnetic resonance imaging) and in the eye's nerves using IVCM (in vivo confocal microscopy). They are also interested in whether these changes can be predicted. The study aims to see if CXL causes acute pain by activating certain nerves and if long-term pain is linked to changes in brain pathways and nerve regrowth. You might be able to join if you are between 8 and 35 years old, have keratoconus and are seeking CXL treatment, or if you are in the same age range without keratoconus. Success for this study means being able to identify and measure these changes in pain pathways and corneal nerves. The current recruitment status is unclear.","Neural activity related to pain and corneal nerve morphology will be measured at 1 year.",143,"Participants will need to be able to lie still for an MRI session lasting 60 minutes.","Not stated in the trial record.",[],"v2"]