TSC Biosample Repository and Natural History Database

NCT05676099 | Recruiting

• 1 other identifier: 15039
• Study Type: observational
• Target: 5,000
• Locations: 2 countries
• Sites: 24

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.

Conditions

Tuberous Sclerosis; Lymphangioleiomyomatosis

Outcome Measures

Primary Outcomes (1)

• Natural History data and biosamples including blood, tissue, or other types of biological samples from individuals with TSC

  The purposes of this project are to: * Collect biosamples such as blood, tissue, fluid, or other types of bodily samples from people with TSC. * Collect information about people with TSC over their lifetime.

  Average 15 years

Interventions

Phlebotomy PROCEDURE

Participants may elect to submit a blood sample to the Biosample Repository.

Buccal (cheek) swab PROCEDURE

Participants may elect to submit a buccal swab sample to the Biosample Repository.

Genetic Testing GENETIC

Biosamples may be processed and analyzed for genetic variants using whole genome sequencing (WGS) or other sequencing methods. Participants whose samples are processed in this manner may be contacted and provided the option to receive TSC1 or TSC2 genetic variant results by opting in using Consent to Return of Genetic Results Form. Participants will be offered a one-time genetic counseling session to review their results, free of charge. CLIA-certified, TSC1 or TSC2 genetic variant results will be returned to participants who opt in to receive such results. Additionally, negative results and results not able to be clinically certified will also be offered to participants with a one-time genetic counseling session to review their results, free of charge using the Return of Genetic Research Results Template Letter. CSS will be responsible for informing clinic participants that their samples have been sequenced and offer to connect participant to the TSC Alliance for further information.

Tissue donation after routine clinical procedure OTHER

Participants may elect to submit a tissue sample to the Biosample Repository following a medical procedure.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

Sponsors & Collaborators

• National Tuberous Sclerosis Association: lead

Study Sites (24)

University of Alabama Birmingham

Birmingham, Alabama, United States

RECRUITING

Loma Linda University Children's Hospital

Loma Linda, California, United States

ACTIVE NOT RECRUITING

University of California Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Jack & Julia Center for TSC, Oakland Children's Hospital and Research Center

Oakland, California, United States

SUSPENDED

The Children's Hospital

Denver, Colorado, United States

ACTIVE NOT RECRUITING

Nicklaus Children's Hospital

Miami, Florida, United States

RECRUITING

Chicago Comer Children's Hospital Neurogenetic Clinic, University of Chicago

Chicago, Illinois, United States

ACTIVE NOT RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

RECRUITING

TSC Alliance

Silver Spring, Maryland, 20910, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

RECRUITING

Minnesota Epilepsy Group

Roseville, Minnesota, United States

RECRUITING

Washington University in St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

New York University Medical Center

New York, New York, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, United States

RECRUITING

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

ACTIVE NOT RECRUITING

Le Bonheur Children's Hospital

Memphis, Tennessee, United States

RECRUITING

Scottish Rite Hospital for Children

Dallas, Texas, United States

RECRUITING

Texas Childrens Hospital Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Memorial Hermann-Texas Medical Center (University of Texas Houston)

Houston, Texas, United States

RECRUITING

Children's National Medical Center

Fairfax, Virginia, United States

RECRUITING

Centre Hospitalier de L'Université de Montréal (Chum)

Montreal, Canada

RECRUITING

Sainte-Justine Université de Montréal

Montreal, Canada

RECRUITING

Related Publications (20)

• 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.

  PMID: 37180419 BACKGROUND

• 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.

  PMID: 39027368 BACKGROUND

• 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.

  PMID: 34087679 BACKGROUND

• 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.

  PMID: 32854808 BACKGROUND

• 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.

  PMID: 32139167 BACKGROUND

• 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.

  PMID: 30103955 BACKGROUND

• 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.

  PMID: 29129154 BACKGROUND

• 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.

  PMID: 27417921 BACKGROUND

• 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.

  PMID: 24754401 BACKGROUND

• 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.

  PMID: 24917535 BACKGROUND

• 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.

  PMID: 22867869 BACKGROUND

• 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.

  PMID: 21079609 BACKGROUND

• 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.

  PMID: 36104799 BACKGROUND

• 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.

  PMID: 22608477 BACKGROUND

• 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.

  PMID: 33897589 BACKGROUND

• 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.

  PMID: 28263820 BACKGROUND

• 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.

  PMID: 33208499 BACKGROUND

• 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.

  PMID: 36793390 BACKGROUND

• 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.

  PMID: 37337371 BACKGROUND

• 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.

  PMID: 38977299 BACKGROUND

Related Links

• TSC Alliance Webpage for Biosample Repository and Natural History Database

Biospecimen

Retention: SAMPLES WITH DNA

Biological materials will be collected at different timepoints in conjunction with procedures that are done for clinical reasons or when consent is given to collect the sample expressly for this research study. Historical cord blood, dried blood spot or placental tissue samples may be collected. Postmortem organ tissue may be collected with consent from the parent/legal guardian of the deceased person with TSC who was enrolled in this protocol or from whom medical records are available to enter relevant clinical data in the NHD. Blood spots may be collected using at-home commercial devices shipped to participants or at CSS using available resources. Blood spots may be created when blood samples arrive at VAI. Biosamples may be processed and analyzed for genetic variants using whole genome sequencing (WGS) or other sequencing methods.

MeSH Terms

Conditions

Tuberous Sclerosis; Lymphangioleiomyomatosis

Interventions

Phlebotomy; Genetic Testing

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Lymphangiomyoma; Neoplasm, Lymphatic Tissue; Neoplasms by Histologic Type; Perivascular Epithelioid Cell Neoplasms; Neoplasms, Connective and Soft Tissue; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Steve Roberds, PhD

  TSC Alliance

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elizabeth Cassidy, MPH

CONTACT

301-562-9890; ecassidy@tscalliance.org

Ayat Abi

CONTACT

aabi@tscalliance.org

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Target Duration: 50 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 9, 2023
• Study Start: January 1, 2016
• Primary Completion (Estimated): December 1, 2050
• Study Completion (Estimated): December 1, 2050
• Last Updated: July 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (22); CA (2)