Cell Collection to Study Eye Diseases

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
ClinicalTrials.gov Identifier:
NCT01432847
First received: September 10, 2011
Last updated: August 6, 2016
Last verified: June 2016
  Purpose

Background:

- Best Vitelliform Dystrophy (Best disease), Late-Onset Retinal Degeneration (L-ORD), and Age-Related Macular Degeneration (AMD) all affect the retina, the light sensing area at the back of the eye. Doctors cannot safely obtain retinal cells to study these diseases. However, cells collected from hair follicles, skin, and blood can be used for research. Researchers want to collect cells from people with Best disease, L-ORD, and AMD, and compare their cells with those of healthy volunteers.

Objectives:

- To collect hair, skin, and blood samples to study three eye diseases that affect the retina: Best disease, L-ORD, and AMD.

Eligibility:

  • Individuals at least 18 years of age who have Best disease, L-ORD, or AMD in at least one eye.
  • Healthy volunteers at least 18 years of age.

Design:

  • The study requires one visit to the National Eye Institute.
  • Participants will be screened with a medical and eye disease history. They will also have an eye exam.
  • Participants will provide a hair sample, a blood sample, and a skin biopsy. The hair will be collected from the back of the head, and the skin will be collected from the inside of the upper arm.

Condition
Retinal Disease
AMD
Retinal Degeneration

Study Type: Observational
Study Design: Time Perspective: Cross-Sectional
Official Title: Generation of Induced Pluripotent Stem (iPS) Cell Lines From Somatic Cells of Participants With Eye Diseases and From Somatic Cells of Matched Controls

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Creation of iPS cells from at least 1 type of somatic tissue collected from participants, differentiation of iPS cells into RPE and/or neural retinal The creation of iPS cells from at least one type of somatic tissue collected from participants. [ Time Frame: Ongoing ] [ Designated as safety issue: No ]

Estimated Enrollment: 930
Study Start Date: August 2011
  Hide Detailed Description

Detailed Description:

This study will establish a repository of biospecimens to generate induced pluripotent stem (iPS) cells, which will be used to determine molecular mechanisms for the following potentially blinding eye diseases: Best Vitelliform Dystrophy (Best Disease); Late-Onset Retinal Degeneration (L-ORD); Age-Related Macular Degeneration (AMD); Leber congenital amaurosis (LCA); Joubert syndrome; X-linked retinitis pigmentosa (RP); oculocutaneous albinism,Stargardt s with ABCA4 gene mutations; Waardenburg syndrome, coloboma, Enhanced S-Cone syndrome (ESCS), Spinocerebellar Ataxia, Type 7 (SCA7) and eye diseases associated with MITF, PAX2, or PAX6 gene mutations. Skin fibroblasts, hair keratinocytes, and/or blood cells may be collected from participants with retinal diseases and from age, gender and ethnicity-matched healthy participants.

Although research involving multiple different ocular cell types from these patients may be performed, the vast majority of the work will be centered on the retinal pigment epithelium (RPE) and neural retina. RPE and/or neural retinal cells generated from the iPS cells of participants with retinal diseases and healthy volunteers will be used to analyze molecular mechanisms involved in disease initiation and progression. In addition, the iPS cell-derived ocular cells will be used to perform high throughput (HTP) drug screens aimed at suppressing the molecular phenotypes of the disease and to identify potential therapeutic agents for these diseases.

Objectives: The primary objective of this study is to generate participant-iPS cells that can be differentiated into ocular cell types, to be used to study the molecular mechanisms of and to develop treatments for Best disease, L-ORD, AMD, LCA, Joubert syndrome, X-linked RP, OCA, Startgardt s disease, Waardenburg syndrome, coloboma, ESCS, SCA7 and eye diseases associated with MITF, PAX2, or PAX6 gene mutations. This objective will be carried out in three phases. First, this study will establish a repository of fibroblasts, keratinocytes, and/or blood cells collected from participants with eye diseases and from matched controls without any eye diseases. Second, the somatic cell repository will be used to generate iPS cells, which will be differentiated into RPE, neural retinal and/or other ocular cells. These cells will be used to elucidate molecular pathways that have led to disease pathogenesis. In the third phase, the participant-specific ocular cells will be used to perform high throughput drug screens to identify novel potential therapeutic compounds. The cells obtained in this protocol may be genetically modified and may be transplanted into animals in the laboratory.

Study Population: We plan to recruit 25 participants with Best disease, 25 participants with L-ORD, 100 participants with AMD, 35 participants with early onset retinal degeneration and/or LCA, 25 participants with Joubert syndrome, 25 participants with X-linked RP, 50 with OCA, 25 with Stargardt s disease with ABCA4 mutations, 25 with eye diseases due to MITF mutations, 25 with Waardenburg syndrome, 25 with eye diseases due to PAX2 mutations, 25 with eye diseases due to PAX6 mutations, 25 participants with coloboma, 5 participants with ESCS without macular edema, 25 participants with SCA7, and 465 healthy volunteers without any eye disease. If possible, unaffected siblings and relatives of participants with eye diseases will be included as healthy volunteers.

Design:In this basic science, research-oriented study, skin, hair, and/or blood samples may be collected from affected participants with the eye diseases and/or genetic mutations under study, and from control participants matched for age, gender and ethnicity. The sample collection procedures will incur only minimal risk to adult participants. For on-site minor participants, the skin biopsy procedure is a minor increment over minimal risk. Offsite minor participants will not undergo the skin biopsy.This study will typically require only one visit by each participant. Participants may be requested to return if their initial sample(s) did not produce adequate cells for study in the laboratory. Participants who were previously enrolled to provide samples for research-grade iPS cell generation may return for an additional visit to provide samples for clinical-grade iPS cell generation, if eligible. The skin fibroblast, keratinocyte, and/or blood samples will then be used to generate participant-specific iPS cells, and these cells will then be differentiated into RPE, neural retinal and/or other ocular cell types. iPS cells may not be made from all samples. The investigators will use the samples for research studies aimed at identifying molecular and signaling pathways underlying disease onset and progression and for developing potential therapeutic treatments for the eye diseases under study.

Outcome Measures: The outcome measures for this study include the creation of iPS cells from at least one of the three types of somatic tissues collected from each participant, the differentiation of iPS cells into RPE, neural retinal cells and/or other ocular cells, and the identification of molecular and physiological phenotypes in these cells that may be linked to the onset or progression of Best disease, L-ORD, AMD, LCA, Joubert syndrome, X-linked RP, OCA, Stargardt s disease, Waardenburg syndrome, coloboma, ESCS, SCA7and eye diseases due to MITF, PAX2, and PAX6 mutations. This analysis may lead to the discovery of therapeutic interventions for these diseases. There are no specific participant-based clinical outcomes for this protocol. Participants will, in general, be seen only once for this protocol, as they will be ascertained and/or receiving standard care under the NEI Evaluation and Treatment Protocol (08-EI-0169) or other NEI protocols. In rare cases, participants may be requested to return to the clinic if their initial sample(s) did not produce adequate cells for study in the laboratory.

  Eligibility

Ages Eligible for Study:   1 Year and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

To be eligible, participants must meet the following inclusion criteria:

  1. Participant has the ability to understand and sign an informed consent.
  2. Participant meets one of the following criteria:

    1. Participant has been diagnosed with Best disease, defined as the presence of lipofuscin-like deposits in the subretinal space and definitive mutations in the BEST1 gene.
    2. Participant has been diagnosed with L-ORD, defined as problems in dark adaptation and the loss of rod and cone function, subretinal deposits, RPE atrophy and hemorrhage, and long anterior zonules in the lens.
    3. Participant has been diagnosed with AMD, defined as the presence of:

    i. large drusen in both eyes along with pigmentary changes with or without advanced AMD (neovascular AMD), or

    ii. geographic atrophy in at least one eye.

    d. Participant has been diagnosed with LCA, defined as a presentation that is typical of the disease and mutations in a known LCA gene. Particular attention will be placed on patients with CRX, CEP290 and NPHP5 mutations, although other genotypes may be collected.

    e. Participant has been diagnosed with Joubert syndrome, defined as the presence of retinal dysfunction and/or degeneration and mutations in a known Joubert gene. Particular attention will be placed on patients with CEP290 or CC2D2A mutations, although other genotypes may be collected.

    f. Participant has been diagnosed with X-linked RP, defined as a presentation that is typical of the disease and mutations in a known X linked RP gene. Particular attention will placed on patients with RPGR or RP2 mutations, although other genotypes may be collected.

    g. Participant diagnosed with oculocutaneous albinism, of any molecular subtype, defined as classic clinical presentation

    h. Participant has been diagnosed with Stargardt's disease, defined as classic clinical presentation with at least one disease causing mutation in the ABCA4 gene.

    i. Participant has been diagnosed with Waardenburg syndrome, defined as classic clinical presentation and/or disease causing mutation in the MITF gene.

    j. Participant has a clinical presentation consistent with the papilorenal syndrome and has a confirmed mutation in the PAX2 gene.

    k. Participant has a clinical presetntation consistent with aniridia and has a confirmed mutation in the PAX6 gene.

    l. Participant has been diagnosed with coloboma, defined as a defect in the iris, neural retina/RPE/choroid and/or optic nerve consistent with a failure of optic fissure closure.

    m. Participant has been diagnosed with ESCS without the presence of macular edema, defined as a combination of 1) a constellation of symptoms including early onset nyctalopia, visual field defects, and possible central vision loss; 2) signs including vitreous degenerative changes and characteristic retinal exam findings; 3) diagnostic electroretinography pattern; and 4) family history of disease.

    n. Participant has been diagnosed with SCA7, as defined by CAG repeat expansion in the ATXN7 gene of greater than 18 repeats. Accrual will be biased towards those with repeat expansion lengths >35, where clinical symptoms are most likely to manifest.

    o. Participant is free of eye diseases and could serve as an unaffected control. Participant s age (within five years), gender, and ethnicity must match an existing participant with one of the eye diseases under study. Control participants matched to AMD participants must not have drusen greater than 63 microns in size.

  3. Adult participant is able to provide a punch skin biopsy and 30 mL of peripheral venous blood OR child participant is able to provide a punch skin biopsy and the lesser of 5 mL/kg or 30 mL of peripheral venous blood. Sampling of ten occipital hairs may be pursued at the investigator s discretion. As a rule, samples will be collected on nonsedated/ anesthetized participants. Sedation/anesthesia will NOT be used solely for the purpose of sample collection. In rare instances where a minor requires sedation for another medically indicated procedure, samples may be collected at the time of sedation/anesthesia. Because young children may not be able to cooperate with sample collection, those unable to provide a skin biopsy and a blood sample may be excluded from the study, based on the judgment of the examining investigator.
  4. Participant meets one of the following criteria:

    1. Participant affected with LCA, Joubert syndrome, RP, OCA, Stargardt s disease, Waardenburg syndrome, coloboma, ESCS, SCA7 or eye disease due to MITF, PAX2, or PAX6 mutations is one year of age or older.
    2. Participant affected with Best disease, L-ORD, or AMD is 18 years of age or older.
    3. Unaffected participant is seven years of age or older and willing and able to provide assent.

EXCLUSION CRITERIA:

A participant is not eligible if any of the following exclusion criteria are present.

  1. Participant is unable to comply with study procedures.
  2. Participant has a systemic disease that, in the opinion of the investigator, compromises the ability to provide adequate samples.

Examples of co-existing diseases that would exclude a participant include a bleeding diathesis or a genetic susceptibility to infections, particularly cutaneous infections.

Additional Criteria for Clinical-Grade Cell Line Generation

The additional eligibility criteria must be met for participants donating samples for the generation of clinical-grade cell lines.

Inclusion Criteria

  1. Participant must be greater than 18 years of age, as of the date of enrollment. There is no upper age limit for donor enrollment.
  2. Participant is able to provide a punch skin biopsy and 100 ml of peripheral venous blood.
  3. Participant is willing and eligible to co-enroll in NEI protocol 15-EI-0128.

Exclusion Criteria

  1. Participant has medical history that includes any of the following:

    1. Thrombocytopenia or other blood dyscrasias
    2. Bleeding diathesis
    3. Antibiotic use within the prior 48 hours
    4. History of cancer
    5. History of exposure to transfusion transmitted diseases including HIV and hepatitis B and C as defined by the Standards for Blood

      Banking and Transfusion Services, American Association of Blood Banks.

    6. Travel to an area where malaria is endemic as defined by the CDC (www.cdc.gov/travel).
    7. At risk for the possible transmission of Creuzefeldt-Jackob Disease (CJD) and Variant Creuzefeldt-Jackob Disease (vCJD) as described in the FDA Guidance for Industry, January 9, 2002, Revised Preventive Measures to Reduce the Possible Risk of Transfusion of Creuzefeldt-Jackob Disease (CJD) and Variant Creuzefeldt-Jackob Disease (vCJD) by Blood and Blood Products
  2. Participant is Febrile (temperature > 38 (Infinite) C).
  3. Participant has Hemoglobin level:

    • African American women <11.5 grams/dL
    • Other women < 12.0 grams/dL
    • Men <12.5 grams/dL
  4. Participant has HCT:

    • African American women < 34%
    • Other women <36%
    • Men <38%
  5. Participant has plateleys <150 x 10(3)/(micro)L
  6. Participant has Absolute neutrophil count <1.0 x 10(3)/microL.
  7. Participant has positive tests for blood borne pathogens (as required by the Standards for Blood Banks and Transfusion Services, American Association of Blood Banks. The currently required tests include anti-HIV1/2, anti-HCV, anti-HBc, Anti-HTLV I/II, anti-T. Cruzi, HBsAg, syphilis, and molecular testing for West Nile virus, HCV, HBV and HIV-1).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01432847

Contacts
Contact: Allison T Bamji, R.N. (301) 451-3437 bamjia@nei.nih.gov
Contact: Brian P Brooks, M.D. (301) 496-3577 brooksb@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
National Eye Institute (NEI)
Investigators
Principal Investigator: Brian P Brooks, M.D. National Eye Institute (NEI)
  More Information

Additional Information:
Publications:
Responsible Party: National Eye Institute (NEI)
ClinicalTrials.gov Identifier: NCT01432847     History of Changes
Other Study ID Numbers: 110245  11-EI-0245 
Study First Received: September 10, 2011
Last Updated: August 6, 2016
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Best Disease
Late-Onset Retinal Degeneration (L-ORD)
Age-Related Macular Degeneration (AMD)
Induced Pluripotent Stem Cell (iPS) Cell Lines
Retinal Degeneration
Age-Related Macular Degeneration
AMD

Additional relevant MeSH terms:
Eye Diseases
Retinal Diseases
Retinal Degeneration

ClinicalTrials.gov processed this record on August 29, 2016