Ignite Creation Date:
2025-12-24 @ 11:38 PM
Ignite Modification Date:
2025-12-29 @ 6:04 AM
Study NCT ID:
NCT04314856
Status:
WITHDRAWN
Last Update Posted:
2022-11-15
First Post:
2020-03-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Novel Clinical Target in Fragile X Syndrome
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D005600', 'term': 'Fragile X Syndrome'}], 'ancestors': [{'id': 'D038901', 'term': 'X-Linked Intellectual Disability'}, {'id': 'D008607', 'term': 'Intellectual Disability'}, {'id': 'D019954', 'term': 'Neurobehavioral Manifestations'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D025064', 'term': 'Sex Chromosome Disorders'}, {'id': 'D025063', 'term': 'Chromosome Disorders'}, {'id': 'D000013', 'term': 'Congenital Abnormalities'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D040181', 'term': 'Genetic Diseases, X-Linked'}, {'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C577112', 'term': '6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo(d)thiazol-2(3H)-one'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '15 male subjects with FXS will be compared to 5 healthy volunteers who will be the control group.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'Principal investigator left institution', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2021-01-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-11', 'completionDateStruct': {'date': '2022-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2022-11-10', 'studyFirstSubmitDate': '2020-03-11', 'studyFirstSubmitQcDate': '2020-03-17', 'lastUpdatePostDateStruct': {'date': '2022-11-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-03-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of concordant readings of regional brain uptake of radiotracer [18F]FTC-146 as a measure of reliability under test-retest conditions', 'timeFrame': 'Up to 6 hours per scan performed on Day 0 (Test) and Day 7 (Retest)', 'description': 'Regional brain uptake of \\[18F\\]FTC-146 will be analyzed by kinetic modeling with metabolite-corrected arterial input functions to establish stability and reproducibility of \\[18F\\] FTC-146 in humans under test and retest conditions.\n\nThis outcome will be assessed in healthy volunteers only.'}, {'measure': 'Difference in Non-displaceable Binding Potential (BPND) of [18F]FTC-146 in fragile X syndrome (FXS) patients relative to healthy volunteers', 'timeFrame': 'Up to 6 hours per scan performed on Day 0 (both groups) and Day 7 (healthy volunteers)', 'description': "Binding potential provides an estimate of the S1R receptor distribution and affinity of \\[18F\\]FTC-146 to the S1R receptors. Binding potential measurements will be compared between participants with fragile X syndrome and control group with healthy volunteers to assess if there is a difference. Binding Potential (BPND) is estimated as the distribution volume ratio (DVR) -1.\n\nDVR's of tracers are used in PET receptor studies where the radiopharmaceutical can be specifically bound to receptors; nonspecifically bound to other macromolecular components, or free in tissue (FT). DVR is calculated using a Logan Plot, which uses the dynamic PET images obtained during imaging and compartment modeling to graphically analyze by linear regression pharmacokinetic data for radiopharmaceuticals that undergo 'reversible' uptake.\n\nHealthy volunteers will have scans at Day 0 and Day 7, and FXS patients will have a single scan on day 0. All scans will be analyzed."}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['FXS'], 'conditions': ['Fragile X Syndrome (FXS)']}, 'referencesModule': {'references': [{'pmid': '30349360', 'type': 'BACKGROUND', 'citation': 'Cipriano PW, Lee SW, Yoon D, Shen B, Tawfik VL, Curtin CM, Dragoo JL, James ML, McCurdy CR, Chin FT, Biswal S. Successful treatment of chronic knee pain following localization by a sigma-1 receptor radioligand and PET/MRI: a case report. J Pain Res. 2018 Oct 12;11:2353-2357. doi: 10.2147/JPR.S167839. eCollection 2018.'}, {'pmid': '28280965', 'type': 'BACKGROUND', 'citation': 'Shen B, Park JH, Hjornevik T, Cipriano PW, Yoon D, Gulaka PK, Holly D, Behera D, Avery BA, Gambhir SS, McCurdy CR, Biswal S, Chin FT. Radiosynthesis and First-In-Human PET/MRI Evaluation with Clinical-Grade [18F]FTC-146. Mol Imaging Biol. 2017 Oct;19(5):779-786. doi: 10.1007/s11307-017-1064-z.'}, {'pmid': '28572487', 'type': 'BACKGROUND', 'citation': 'Hjornevik T, Cipriano PW, Shen B, Park JH, Gulaka P, Holley D, Gandhi H, Yoon D, Mittra ES, Zaharchuk G, Gambhir SS, McCurdy CR, Chin FT, Biswal S. Biodistribution and Radiation Dosimetry of 18F-FTC-146 in Humans. J Nucl Med. 2017 Dec;58(12):2004-2009. doi: 10.2967/jnumed.117.192641. Epub 2017 Jun 1.'}]}, 'descriptionModule': {'briefSummary': 'Fragile X syndrome (FXS) is the most common genetic cause of autism spectrum disorder (ASD). The investigators wish to examine brain distribution of sigma-1 receptors in young adult males with FXS using 18F-FTC-146 PET. This project will study the distribution of sigma-1 receptors in 15 young (18-30 years) male adults with FXS compared to 5 healthy adult volunteers.', 'detailedDescription': 'In this study, we measured sigma-1 receptor density in the regions of interest in brain known to be involved in executive functioning and cognition using 18F-FTC-146 PET. We then compared S1R density in areas ROIs not involved in executive functioning and cognition. This provided a framework for predicting functional impairment based on brain-behavior relationships.\n\nThe study had two aims. The first aim was to evaluate the reliability of 18F-FTC-146 brain uptake in healthy controls under test and retest conditions to establish a baseline measure of S1R density and quantify regional brain uptake of radiotracer in five healthy adults. The second aim was to characterize S1R density in brains of young adult males with FXS which will then be compared to healthy volunteers.\n\nThis was the very first PET study to image sigma-1 receptor density in participants with fragile X syndrome, thereby testing whether altered receptor density is present in brain in fragile X syndrome patients when compared to healthy volunteers. If confirmed, the current study would have provided compelling clinical-translational support for an important pathophysiological mechanism of cognition and executive function. The study had considerable potential for advancing the neurobiological understanding of fragile X syndrome in humans.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'genderBased': True, 'genderDescription': 'For FXS only: Participants must be male adults between 18 and 30 years with Fragile X-syndrome', 'healthyVolunteers': True, 'eligibilityCriteria': "INCLUSION CRITERIA\n\nInclusion criteria for healthy volunteers:\n\n1. Ages 18-65\n2. Either gender and all ethno-racial categories\n3. Capacity to provide informed consent\n4. Female participants are expected to use an effective method of birth control throughout the study which includes: hormonal methods (birth control pills, patches, injections, vaginal ring or implants), barrier method (condom or diaphragm) used with spermicide, intrauterine device (IUD), or abstinence (no sex)\n5. Can travel to Stanford for 2 scan days.\n\nInclusion criteria for individuals with FXS:\n\n1. Males who are physically healthy\n2. Aged between 18 and 30 years inclusive\n3. Can travel to Stanford for a 2-day visit.\n4. IQ between 40 and 80 points.\n5. Ability to remain seated for more than 10 minutes.\n6. Have an established genetic diagnosis of FXS (full mutation with evidence of aberrant methylation of the FMR1 gene, confirmed by genetic testing).\n\nEXCLUSION CRITERIA\n\nExclusion criteria for healthy volunteers:\n\n1. Any current or lifetime psychiatric diagnosis\n2. Current or past use of psychotropic medication for purposes of treating a mental illness\n3. Pregnant or nursing females\n4. Major medical or neurological problem, including anemia (Hb , 12 g/dl in women and \\<14 g/dl in men) (e.g., unstable hypertension, seizure disorder, head trauma)\n5. Current diagnosis of vasculopathy or Raynouds\n6. Participant is unable to tolerate being off of anticoagulant medication during study\n7. Positive urine screen for illicit drugs\n8. Presence of metal in the body that is contraindicated for MRI scans\n9. Current exposure to radiation in the workplace, or history of participation in nuclear medicine procedures does not exceed defined annual limits\n10. Stanford University student status (i.e., we will exclude students such as undergrads, grad students and postdocs that currently attend at Stanford University)\n\nExclusion criteria for individuals with FXS:\n\n1. Any contraindication for MRI scanning procedures (metal in body, braces, claustrophobia, etc.)\n2. No history of with substance abuse, traumatic brain injury and\n3. BMI greater than 18.5\n4. Diagnosis of a known genetic disorder (other than FXS).\n5. Active medical problems such as unstable seizures, congenital heart disease, endocrine disorders.\n6. Significant sensory impairments such as blindness or deafness.\n7. DSM-5 diagnosis of other severe psychiatric disorder such as bipolar disorder or schizophrenia.\n8. Pre-term birth (\\<34 weeks' gestation) or low birth weight (\\<2000g).\n9. Current use of benzodiazepines. Individuals who are taking concomitant psychoactive medications will be tracked and examined in post-hoc analyses, given that it is extremely difficult to recruit individuals who are medication-free or who are willing to go off those medications prior to entering the study.\n10. Current exposure to radiation in the workplace, or history of participation in nuclear medicine procedures does not exceed defined annual limits"}, 'identificationModule': {'nctId': 'NCT04314856', 'briefTitle': 'Novel Clinical Target in Fragile X Syndrome', 'organization': {'class': 'OTHER', 'fullName': 'Stanford University'}, 'officialTitle': 'Sigma-1 Receptors: A Novel Clinical Target in Fragile X Syndrome', 'orgStudyIdInfo': {'id': 'IRB 50016'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Fragile X Syndrome', 'description': 'Adult males aged 18-30 years diagnosed with FXS will undergo a PET/MRI scan using 18F-FTC-146 to determine sigma-1 receptor density.\n\nThese participants will only be administered once with 18F-FTC-146.', 'interventionNames': ['Drug: 18F-FTC-146']}, {'type': 'EXPERIMENTAL', 'label': 'Healthy Volunteers (Control)', 'description': 'Adults aged 18-65 years undergo a PET/MRI scan using 18F-FTC-146 to determine sigma-1 receptor density.\n\nTest-retest studies will be performed where these individuals will each be injected twice with 18F-FTC-146.', 'interventionNames': ['Drug: 18F-FTC-146']}], 'interventions': [{'name': '18F-FTC-146', 'type': 'DRUG', 'otherNames': ['FTC146'], 'description': '18F-FTC-146 is a PET radiopharmaceutical that can be used to determine sigma-1 receptor density.', 'armGroupLabels': ['Fragile X Syndrome', 'Healthy Volunteers (Control)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94305', 'city': 'Stanford', 'state': 'California', 'country': 'United States', 'facility': 'Stanford University', 'geoPoint': {'lat': 37.42411, 'lon': -122.16608}}], 'overallOfficials': [{'name': 'Guido Davidzon, MD SM', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Stanford University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Guido A. Davidzon, MD, SM', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Associate Professor of Radiology/Nuclear Medicine & Molecular Imaging', 'investigatorFullName': 'Guido A. Davidzon, MD, SM', 'investigatorAffiliation': 'Stanford University'}}}}