TSC Biosample Repository and Natural History Database

Tuberous Sclerosis Clinical Trial

Official title:

TSC Alliance Tuberous Sclerosis Complex (TSC) Biosample Repository and Natural History Database

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05676099
• Other study ID #: 15039
• Status: Recruiting
• Start date: January 2016
• Est. completion date: December 2050

Study information

• Verified date: February 2024
• Source: National Tuberous Sclerosis Association
• Contact: Elizabeth Cassidy, MPH
• Phone: 301-562-9890
• Email: ecassidy[@]tscalliance.org
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: December 2050
• Est. primary completion date: December 2050
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

-

Related Conditions & MeSH terms

• Lymphangioleiomyomatosis
• Sclerosis
• Tuberous Sclerosis

Intervention

Procedure:
• Phlebotomy
Participants may elect to submit a blood sample to the Biosample Repository.
• Buccal (cheek) swab
Participants may elect to submit a buccal swab sample to the Biosample Repository.

Genetic:
• Genetic Testing
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.

Other:
• Tissue donation after routine clinical procedure
Participants may elect to submit a tissue sample to the Biosample Repository following a medical procedure.

Locations

Country	Name	City	State
Canada	Centre Hospitalier de L'Université de Montréal (Chum)	Montréal
Canada	Sainte-Justine Université de Montréal	Montréal
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Chicago Comer Children's Hospital Neurogenetic Clinic, University of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Texas Scottish Rite Hospital for Children	Dallas	Texas
United States	The Children's Hospital	Denver	Colorado
United States	Children's National Medical Center	Fairfax	Virginia
United States	Memorial Hermann-Texas Medical Center (University of Texas Houston)	Houston	Texas
United States	Texas Childrens Hospital Baylor College of Medicine	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Loma Linda University Children's Hospital	Loma Linda	California
United States	University of California Los Angeles	Los Angeles	California
United States	Le Bonheur Children's Hospital	Memphis	Tennessee
United States	Nicklaus Children's Hospital	Miami	Florida
United States	New York University Medical Center	New York	New York
United States	Jack & Julia Center for TSC, Oakland Children's Hospital and Research Center	Oakland	California
United States	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania
United States	Minnesota Epilepsy Group	Roseville	Minnesota
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	TSC Alliance	Silver Spring	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Tuberous Sclerosis Association

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (18)

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. — View 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. — View 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. — View 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. — View 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. Erratum In: Mol Psychiatry. 2012 Apr;17(4):469. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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