Bellingham, Virginia

TSC Biosample Repository and Natural History Database

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.

Product Surveillance Registry

Product Performance Report: Evaluate Long-term Reliability & Performance of Medtronic Marketed Cardiac Therapy Products

All Medtronic market-released leads and all market-released IPG, ICD and CRT devices are eligible to be included in this study.

Biomarkers Related to Bone in Pediatric Gaucher Disease

Gaucher disease (GD), the most common lysosomal storage disorder, is caused by a deficiency of the enzyme glucocerebrosidase. Clinically, there are three sub-types according to neurological involvement. Type 1 GD (GD1) is non-neuronopathic GD, and GD types 2 and 3 (GD2-3) are neuronopathic forms. Bone involvement includes skeletal structural abnormalities such as Erlenmeyer flask deformities, cystic changes, growth retardation, progressive kyphoscoliosis, osteonecrosis, bone density abnormalities, bone fragility, and pathological fractures occur at a spectrum in different GD clinical types. While bone crises are rare (often referred to as Gaucher crises), avascular necrosis (AVN) may occur in the pediatric age group with long-term morbidity and is often associated with chronic pain and orthopedic deformities requiring multiple surgical interventions. As known, the development of the skeleton development (longitudinal and bone mass growth) is subject to both environmental and genetic influences. During childhood, skeletal growth is characterized by rapid bone growth and continues to lengthen bones by adding bone tissue on the epiphyseal plate until adolescence. The thickening of long bones is processed by adding bony tissue to its surface. The process of bone remodeling and repair continues after birth and adulthood. Bone marrow infiltration and bone remodeling defects termed "Erlenmeyer flask deformity" are the most common GD-related bone diseases. Without intervention directed at GD, bone involvement usually starts before puberty. Moreover, children with severe GD present retarded growth and delayed puberty (<5th percentile in 34% of children). However, the underlying mechanisms of regulation of bone development and related complications in the pediatric age group in GD are not yet fully known. Neither the bone-specific biomarkers nor their relationship regarding growth factors associated with normal bone turnover during the normal growth process have been studied in detail in GD in the pediatric age group. Abnormalities in skeletal growth and bone turnover may be related to the abnormal regulation of some growth factors, for example, the elevation of fibroblast growth factor 23 (FGF23) or inhibition of insulin-like growth factors (IGFs) resulting in bone growth impartment. Moreover, chronic inflammation leads to alterations in the function and differentiation of osteoclasts and osteoblasts, which participate in bone growth and remodeling. Furthermore, the evaluation of bone involvement could be challenging for the pediatric age group. The marrow replacement due to GD that moves in the opposite direction with the expected disappearance of the red marrow makes it challenging to evaluate the bone marrow using MRI and requires experience and technical skills to interpret the imaging studies. In addition, the technique of bone density evaluation is still not uniform in children, especially for different age groups.

Safety, PK/PD, and Exploratory Efficacy Study of AMT-191 in Classic Fabry Disease

AMT-191 is an investigational gene therapy that encodes a recombinant serotype 5 based adeno-associated viral vector (rAAV5). AMT-191 is designed to deliver a liver-specific expression of the transgene coding for human a-galactosidase A gene (GLA) to Fabry patients via a single (one-time) IV infusion. Delivery of AMT-191 to the systemic circulation is expected to result in a therapeutic effect by promoting the liver expression of the lysosomal enzyme GLA in plasma and leukocytes levels in patients with FD Fabry disease (FD).

Phase 3 Study of Toripalimab Alone or in Combination With Tifcemalimab as Consolidation Therapy in Patients With Limited-stage Small Cell Lung Cancer (LS-SCLC)

A Study About Antibody Levels and Biomarkers in the Blood in People With Late-onset Pompe Disease

No investigational drug will be administered to participants in this study. Blood and urine will be collected as part of the study. The duration of the study is approximately 2 years, participants may withdraw at any time.

PrEP Intervention Among Black Sexual Minority Men

Black gay, bisexual, and other Black sexual minority men (BSMM) are a priority population and experience the highest rate of new HIV infections in the United States. Maryland (MD) is an HIV epicenter and ranks 4th in AIDS cases nationally; the state has several hotspots of HIV and AIDS cases in geographically distinct areas, including urban, suburban, and rural settings. Prince George's (PG) County is a majority Black suburban county (63% Black) bordering Washington, DC, with the highest per capita income for Black people in the nation, yet the second highest incidence and prevalence of HIV in the DC greater metropolitan area. It is an understudied region in the "Ending the Epidemic" initiative to end HIV in the United States. Despite the availability of PrEP for prevention and overall economic resources in this area, uptake among BSMM remains low. Greater understanding of factors impacting PrEP utilization among BSMM in this population and region of the U.S. are necessary for successful HIV prevention for BSMM. Additionally, extant literature specific to PrEP use among BSMM in PG county is extremely limited. Internalized racism is an important and understudied factor that can deter PrEP use among BSMM, similar to the well documented associations between internalized homophobia and several HIV risk behaviors among SMM. Research has consistently shown the impact of racism and homophobia on several HIV-related outcomes among SMM, including HIV stigma that deters uptake of HIV prevention. In contrast, social support can facilitate HIV prevention behaviors among BSMM. Internalized racism/homophobia, HIV stigma, and peer social support are potentially modifiable factors that may directly impact PrEP acceptability and PrEP stigma among BSMM; the associations between internalized stigma and PrEP use among BSMM are still notably understudied. Despite this, interventions promoting PrEP use among BSMM have largely not addressed internalized stigma as a potential barrier to uptake. Notably, internalized racism/homophobia is more modifiable than experienced or anticipated racism/homophobia. The goal of the proposed research is to design a peer-based community intervention focused on addressing internalized homophobia, internalized racism, HIV stigma, and peer BSMM support to increase PrEP initiation among BSMM in Prince George's County, MD. The investigators will adapt the MPowerment peer-based model: This is a CDC-developed evidence-based intervention originally designed to reduce sexual risk and improve peer support among SMM through the use of peer-led activities and discussions, often in a drop-in center that is a safe space for young BSMM.31,32 There have been several successful adaptations of the MPowerment model in different settings of SMM. The investigators are adapting the model to focus on improving PrEP initiation among BSMM, through focusing on peer BSMM support, and reducing internalized racism, homophobia, and HIV stigma through peer-led events and activities. The following are our aims: Aim 1. Using ethnographic methods (participant and direct observation), study peer-peer interactions/exchanges and HIV prevention communications among BSMM in two ongoing MPowerment programs, one in Falls Church, VA (suburban) and the other in Washington, DC (urban). As the PI is a BSMM well connected to these organizations, he has unique advantages in conducting these ethnographies. Aim 2. Conduct 32 in depth interviews to inform adapting an MPowerment intervention to reduce internalized racism/homophobia and increase PrEP uptake among BSMM in PG County. This would inform intervention site selection, promotion materials, and design of events and activities. Aim 3. Pilot test a community-based pretest-posttest intervention (n=130) to increase PrEP uptake among BSMM in PG County, based on the MPowerment model, with a focus on reducing internalized racism/ homophobia/HIV stigma, and increasing social support and resilience.

Assess Urine Biomarkers to Predict Nephropathy in Fabry Disease

This is a study to assess the markers related to autophagy, apoptosis, pyroptosis, and inflammatory markers related to NFkB, TNF-alpha, and TGF-β1 pathways in the urine. Urinary biomarkers will then be compared to the standard measures of kidney function and proteinuria: GFR, cystatin-C, B2M, bikunin, NGAL. Gb3 and Lyso-Gb3, urine microalbumin, and urine protein-to-creatinine (UPCR) ratio. Investigators will also analyze the role of therapy, especially for the inflammatory responses in participants on stable enzyme replacement therapy (ERT) with that of patients naïve to therapy. There will be a total of 25 biomarkers that will be assessed during the study. Biomarkers of inflammation 1. Il-4 2. Il-6 3. IL-8 4. Il-10 5. Il-12 6. Il-18 7. MCP1 8. TGF-β1 9. IFN-γ 10. TNF-α 11. IL-1β 12. RANTES 13. BAFF 14. APRIL 15. PAI-1 Biomarkers of kidney function and proteinuria 16. B2M 17. Bikunin 18. NGAL 19. Osteopontin 20. Clusterin 21. Creatinine Acute kidney injury 22. KIM-1 23. YKL-40 24. EGF 25. CK-18 M30

The Natural History Study of Patients With Sanfilippo Disease(s) (MPS3)

This is a natural history study of patients with Sanfilippo Disease (MPS3). Patients will be followed over the course of 6 months in which they have blood and urine collected, hearing assessment, complete questionnaires and are evaluated by the Principal Investigator.