Cell-Based Approaches For Modeling and Treating Ataxia-Telangiectasia

NCT02246491 | Terminated DMC

• 2 other identifiers: IRB00038916J1491
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to better understand the causes of the disease Ataxia-Telangiectasia and, in the longer-term, develop new therapies for the disease using stem cells. Induced pluripotent stem cells (iPSC) are a type of cells that can be made in the laboratory from cells in your body, such as blood cells or skin cells (fibroblasts). These stem cells can then be used for research purposes. For example, stem cells can be used to investigate how the mutation in ATM causes the actual symptoms of Ataxia-Telangiectasia. In addition, the stem cells can be used to screen for drugs that could be helpful to treat the disease or to develop new laboratory techniques to correct the mutation that causes Ataxia-Telangiectasia. where the mutation that causes the disease is corrected by the investigators. The stem cells generated in this study will not be used directly for patient therapy and therefore this research does not have a direct benefit to you. However, it will help advance our understanding of the disease and develop future therapies. Patients who enroll in this study will get all of the standard therapy they would get for their tumor whether or not they participate in this study. There is no extra or different therapy given. The study involves a one-time procedure (either blood collection or skin biopsy).

Conditions

Ataxia-Telangiectasia (A-T)

Outcome Measures

Primary Outcomes (1)

• Number of samples of primary A-T fibroblast samples that can be successfully reprogrammed to iPSCs

  Fibroblasts from patients with A-T will be collected for eligible, consenting participants and processed for reprogramming and iPSC analysis in the laboratory

  2 years

Secondary Outcomes (2)

• Number of samples of patient A-T fibroblasts that can be reprogrammed to iPSCs with and without gene correction

  2 years

• Quantification of the cloning efficiency of primary cells haploinsufficient for ATM relative to healthy controls

  2 years

Study Arms (2)

iPSCs without gene correction

OTHER

This is not a clinical trial and there is no immediate benefit to the participants. At this time, iPSCs and their derived products are not suitable for administration to patients. However, they are useful for basic and preclinical studies of the disease, such as mechanistic studies of ATM function or screening for small molecules with therapeutic value. As regenerative medicine continues to advance, iPSCs and their products may ultimately be used for clinical studies aimed at replacing damaged tissues in A-T patients.

Other: Carrier patients iPS cell line

iPSCs with gene correction

OTHER

This is not a clinical trial and there is no immediate benefit to the participants. At this time, iPSCs and their derived products are not suitable for administration to patients. However, they are useful for basic and preclinical studies of the disease, such as mechanistic studies of ATM function or screening for small molecules with therapeutic value. As regenerative medicine continues to advance, iPSCs and their products may ultimately be used for clinical studies aimed at replacing damaged tissues in A-T patients.

Other: A-T iPS cell line

Interventions

A-T iPS cell line OTHER

Reprogramming A-T patients iPS cell line

iPSCs with gene correction

Carrier patients iPS cell line OTHER

Reprogramming iPS cell line from carrier patients

iPSCs without gene correction

Eligibility Criteria

• Age: 3 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients that meet the classic diagnosis of A-T and for whom the underlying mutation(s) is known. The diagnosis of A-T has been made by the clinician using the following criteria:
• Characteristic neurological abnormalities, including but not limited to oculomotor apraxia, bulbar dysfunction, postural instability, and ataxia.
• Presence of telangiectasia on the conjunctivae and/or skin.
• Laboratory abnormalities including but not limited to elevated serum alpha-feto- protein, level, absence of ATM on western blot, increased x-ray induced chromosomal breakage in comparison to a control population, mutations in both alleles of the ATM gene. Parents of the patients above, who are haploinsufficient and whose mutation is known.

You may not qualify if:

• Patients under 2 years of age No subjects will be excluded on the basis of age, sex, race, or socio-economic status.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

SKCCC at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Ataxia Telangiectasia

Condition Hierarchy (Ancestors)

Spinocerebellar Ataxias; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Ataxia; Dyskinesias; Neurologic Manifestations; Telangiectasis; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Primary Immunodeficiency Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Sonia Franco, M.D.

  SKCCC at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2014
• First Posted: September 22, 2014
• Study Start: February 3, 2015
• Primary Completion: July 5, 2018
• Study Completion: July 5, 2018
• Last Updated: March 19, 2019

Record last verified: 2019-03

Locations

US (1)