Clinical trial NCT05676099: TSC Biosample Repository and Natural History Database
Official title: TSC Alliance Tuberous Sclerosis Complex (TSC) Biosample Repository and Natural History Database
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Tuberous Sclerosis
Lymphangioleiomyomatosis
Lead sponsor: National Tuberous Sclerosis Association
Sponsor class: OTHER
First posted: 2023-01-09
Enrollment: 5000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: An individual must have a diagnosis of tuberous sclerosis complex, based on the current clinical and genetic diagnostic criteria. The individual may enroll if they have a diagnosis of sporadic LAM. All persons with tuberous sclerosis complex are eligible to participate, such as individuals with limited decisional capacity.

Brief summary: The TSC Biosample Repository collects and stores samples of blood, DNA, and tissues that scientists can request to use in their research. The samples we collect are all linked to clinical data in the TSC Natural History Database. The TSC Natural History Database captures clinical data to document the impact of the disease on a person's health over his or her lifetime. This data may be collected retrospectively or prospectively.

Detailed description: The purpose of the project which is sponsored by the TSC Alliance is to learn more about tuberous sclerosis complex (TSC) which may lead to new treatments for conditions that affect different areas of the body such as the brain, kidney, heart, lungs, and skin. The TSC Alliance TSC Biosample Repository (BSR) was established to provide a central biobank at the Van Andel Institute (VAI) Biorepository in Grand Rapids, Michigan for the collection of blood, tissues, and cells from a vast number of individuals with TSC.

The TSC Alliance Natural History Database (NHD), established in 2006, will serve as the central repository of de-identified clinical data associated with biosamples collected from individuals with TSC. The NHD research project involves collection of retrospective and prospective private information on individuals with a diagnosis of TSC over their lifespan (i.e., a longitudinal study). The VAI Biorepository will distribute biosamples and NHD data to researchers as approved by the TSC Alliance.

This project also aims to collect biosamples and clinical data on people affected by sporadic lymphangioleiomyomatosis (sporadic LAM). LAM is a common symptom reported in TSC that may occur outside the context of a TSC diagnosis (i.e., sporadic LAM patients).

The collection of biosamples will be at a clinical study site (CSS) such as a TSC Alliance recognized TSC clinic, a non-CSS such as a participant's home, an educational meeting, or by other clinical partners (CP) with institutional review board (IRB) approval of this protocol and informed consent forms. Collection of biosamples may also occur at a non-CSS or by a licensed phlebotomist (e.g., via partnership with mobile phlebotomy companies). The VAI Biorepository will provide collection kits, instructions, and materials to the CSS, non-CSS, CP, or directly to participant.

The CSS, CP, non-CSS, or authorized representative will ship collected biosamples to the VAI Biorepository for processing and storage according to their IRB-approved standard operating procedures. The VAI Biorepository will distribute biosamples to investigators as approved by the TSC Alliance. Their accreditation under the Biorepository Accreditation Program of the College of American Pathologists (CAP) will stand as the governing rules for best practices. Distribution of biosamples will require receipt of the investigator's IRB approval and a material transfer agreement (MTA) executed between the approved investigator and the TSC Alliance.

Clinical data in the NHD associated with a biosample will be provided to an investigator as approved by the Natural History Database-Biosample Repository (NHD-BSR) Steering Committee.

This project is open to individuals of all ages with a diagnosis of tuberous sclerosis complex or lymphangioleiomyomatosis.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of tuberous sclerosis complex or lymphangioleiomyomatosis (sporadic LAM).

Exclusion Criteria:

-

Primary outcomes:
measure: Natural History data and biosamples including blood, tissue, or other types of biological samples from individuals with TSC
timeFrame: Average 15 years
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda University Children's Hospital
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Oakland
country: United States
facility: Jack & Julia Center for TSC, Oakland Children's Hospital and Research Center
state: California
city: Denver
country: United States
facility: The Children's Hospital
state: Colorado
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Chicago Comer Children's Hospital Neurogenetic Clinic, University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Silver Spring
country: United States
facility: TSC Alliance
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Roseville
country: United States
facility: Minnesota Epilepsy Group
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Dallas
country: United States
facility: Texas Scottish Rite Hospital for Children
state: Texas
city: Houston
country: United States
facility: Texas Childrens Hospital Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Memorial Hermann-Texas Medical Center (University of Texas Houston)
state: Texas
city: Fairfax
country: United States
facility: Children's National Medical Center
state: Virginia
city: Montréal
country: Canada
facility: Centre Hospitalier de L'Université de Montréal (Chum)
city: Montréal
country: Canada
facility: Sainte-Justine Université de Montréal
Study officials:
References:
citation: Pounders AJ, Rushing GV, Mahida S, Nonyane BAS, Thomas EA, Tameez RS, Gipson TT. Racial differences in the dermatological manifestations of tuberous sclerosis complex and the potential effects on diagnosis and care. Ther Adv Rare Dis. 2022 Dec 10;3:26330040221140125. doi: 10.1177/26330040221140125. eCollection 2022 Jan-Dec.
citation: Rubtsova VI, Chun Y, Kim J, Ramirez CB, Jung S, Choi W, Kelly ME, Lopez ML, Cassidy E, Rushing G, Aguiar DJ, Lau WL, Ahdoot RS, Smith M, Edinger AL, Lee SG, Jang C, Lee G. Circulating biomarkers of kidney angiomyolipoma and cysts in tuberous sclerosis complex patients. iScience. 2024 Jun 13;27(7):110265. doi: 10.1016/j.isci.2024.110265. eCollection 2024 Jul 19.
citation: Parthasarathy S, Mahalingam R, Melchiorre J, Harowitz J, Devinsky O. Mortality in tuberous sclerosis complex. Epilepsy Behav. 2021 Aug;121(Pt A):108032. doi: 10.1016/j.yebeh.2021.108032. Epub 2021 Jun 1.
citation: Chivukula S, Modiri O, Kashanian A, Babayan D, Ibrahim GM, Weil AG, Tu A, Wu JY, Mathern GW, Fallah A. Effect of Gene Mutation on Seizures in Surgery for Tuberous Sclerosis Complex. Can J Neurol Sci. 2021 May;48(3):327-334. doi: 10.1017/cjn.2020.185. Epub 2020 Aug 28.
citation: Gupta A, de Bruyn G, Tousseyn S, Krishnan B, Lagae L, Agarwal N; TSC Natural History Database Consortium. Epilepsy and Neurodevelopmental Comorbidities in Tuberous Sclerosis Complex: A Natural History Study. Pediatr Neurol. 2020 May;106:10-16. doi: 10.1016/j.pediatrneurol.2019.12.016. Epub 2020 Feb 4.
citation: Song J, Swallow E, Said Q, Peeples M, Meiselbach M, Signorovitch J, Kohrman M, Korf B, Krueger D, Wong M, Sparagana S. Epilepsy treatment patterns among patients with tuberous sclerosis complex. J Neurol Sci. 2018 Aug 15;391:104-108. doi: 10.1016/j.jns.2018.06.011. Epub 2018 Jun 15.
citation: Jeong A, Nakagawa JA, Wong M. Predictors of Drug-Resistant Epilepsy in Tuberous Sclerosis Complex. J Child Neurol. 2017 Dec;32(14):1092-1098. doi: 10.1177/0883073817737446.
citation: Jeong A, Wong M. Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex. Epilepsia. 2016 Sep;57(9):1443-9. doi: 10.1111/epi.13467. Epub 2016 Jul 15.
citation: Kothare SV, Singh K, Hochman T, Chalifoux JR, Staley BA, Weiner HL, Menzer K, Devinsky O. Genotype/phenotype in tuberous sclerosis complex: associations with clinical and radiologic manifestations. Epilepsia. 2014 Jul;55(7):1020-4. doi: 10.1111/epi.12627. Epub 2014 Apr 22.
citation: Kothare SV, Singh K, Chalifoux JR, Staley BA, Weiner HL, Menzer K, Devinsky O. Severity of manifestations in tuberous sclerosis complex in relation to genotype. Epilepsia. 2014 Jul;55(7):1025-9. doi: 10.1111/epi.12680. Epub 2014 Jun 10.
citation: van Eeghen AM, Nellist M, van Eeghen EE, Thiele EA. Central TSC2 missense mutations are associated with a reduced risk of infantile spasms. Epilepsy Res. 2013 Jan;103(1):83-7. doi: 10.1016/j.eplepsyres.2012.07.007. Epub 2012 Aug 3.
citation: Ehninger D, Sano Y, de Vries PJ, Dies K, Franz D, Geschwind DH, Kaur M, Lee YS, Li W, Lowe JK, Nakagawa JA, Sahin M, Smith K, Whittemore V, Silva AJ. Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice. Mol Psychiatry. 2012 Jan;17(1):62-70. doi: 10.1038/mp.2010.115. Epub 2010 Nov 16.
citation: Boggarapu S, Roberds SL, Nakagawa J, Beresford E. Characterization and management of facial angiofibroma related to tuberous sclerosis complex in the United States: retrospective analysis of the natural history database. Orphanet J Rare Dis. 2022 Sep 14;17(1):355. doi: 10.1186/s13023-022-02496-2.
citation: Aronow ME, Nakagawa JA, Gupta A, Traboulsi EI, Singh AD. Tuberous sclerosis complex: genotype/phenotype correlation of retinal findings. Ophthalmology. 2012 Sep;119(9):1917-23. doi: 10.1016/j.ophtha.2012.03.020. Epub 2012 May 16.
citation: Mowrey K, Northrup H, Rougeau P, Hashmi SS, Krueger DA, Ebrahimi-Fakhari D, Towbin AJ, Trout AT, Capal JK, Franz DN, Rodriguez-Buritica D. Frequency, Progression, and Current Management: Report of 16 New Cases of Nonfunctional Pancreatic Neuroendocrine Tumors in Tuberous Sclerosis Complex and Comparison With Previous Reports. Front Neurol. 2021 Apr 9;12:627672. doi: 10.3389/fneur.2021.627672. eCollection 2021.
citation: Swallow E, King S, Song J, Peeples M, Signorovitch JE, Liu Z, Prestifilippo J, Frost M, Kohrman M, Korf B, Krueger D, Sparagana S. Patterns of Disease Monitoring and Treatment Among Patients With Tuberous Sclerosis Complex-related Angiomyolipomas. Urology. 2017 Jun;104:110-114. doi: 10.1016/j.urology.2017.02.036. Epub 2017 Mar 2.
citation: Hsieh LS, Wen JH, Nguyen LH, Zhang L, Getz SA, Torres-Reveron J, Wang Y, Spencer DD, Bordey A. Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice. Sci Transl Med. 2020 Nov 18;12(570):eabc1492. doi: 10.1126/scitranslmed.abc1492.
citation: Giannikou K, Martin KR, Abdel-Azim AG, Pamir KJ, Hougard TR, Bagwe S, Tang Y, MacKeigan JP, Kwiatkowski DJ, Henske EP, Lam HC. Spectrum of germline and somatic mitochondrial DNA variants in Tuberous Sclerosis Complex. Front Genet. 2023 Jan 30;13:917993. doi: 10.3389/fgene.2022.917993. eCollection 2022.
citation: Bhaoighill MN, Falcon-Perez JM, Royo F, Tee AR, Webber JP, Dunlop EA. Tuberous Sclerosis Complex cell-derived EVs have an altered protein cargo capable of regulating their microenvironment and have potential as disease biomarkers. J Extracell Vesicles. 2023 Jun;12(6):e12336. doi: 10.1002/jev2.12336.
citation: Loubert F, House AA, Larochelle C, Major P, Keezer MR. Development and internal validation of a clinical risk score to predict incident renal and pulmonary tumours in people with tuberous sclerosis complex. J Med Genet. 2024 Sep 24;61(10):943-949. doi: 10.1136/jmg-2023-109717.