Trial record 2 of 36 for:    brian p brooks

Cell Collection to Study Eye Diseases

This study is currently recruiting participants.
Verified June 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01432847
First received: September 10, 2011
Last updated: March 14, 2014
Last verified: June 2013

September 10, 2011
March 14, 2014
August 2011
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Complete list of historical versions of study NCT01432847 on ClinicalTrials.gov Archive Site
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Cell Collection to Study Eye Diseases
Generation of Induced Pluripotent Stem (iPS) Cell Lines From Somatic Cells of Participants With Eye Diseases and From Somatic Cells of Matched Controls

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.

This study will establish a repository of biospecimens to generate induced pluripotent (iPS) stem cells to be used to determine molecular mechanisms for three potentially blinding retinal diseases: Best Vitelliform Dystrophy (Best Disease), Late-Onset Retinal Degeneration (L-ORD), and Age-Related Macular Degeneration (AMD). Skin fibroblasts, hair keratinocytes, and CD34+ blood cells will be collected from participants with Best Disease, L-ORD, and AMD and from age, gender and ethnicity-matched healthy participants.

Retinal pigment epithelium (RPE) cells generated from the iPS cells of patient and healthy volunteers will be used to analyze molecular mechanisms involved in disease initiation and progression. In addition, the iPS cell-derived RPE cells will be used to perform high throughput (HTP) drug screens aimed at suppressing the molecular phenotypes of the disease to identify potential therapeutic agents for Best disease, L-ORD, and AMD.

OBJECTIVES:

The primary objective of this study is to generate participant-specific RPE cells to be used to study the molecular mechanisms of and to develop treatments for Best disease,

L-ORD and AMD. This objective will be carried out in three phases. First, this study will establish a repository for fibroblasts, keratinocytes, and CD34+ blood cells collected from participants with these three diseases and from participants without any retinal diseases. Second, the somatic cell repository will be used to generate iPS cells, which will be differentiated into RPE cells. These RPE cells will be used to elucidate molecular pathways that have led to disease pathogenesis. In the third phase, the patient-specific RPE cells will be used to perform high throughput drug screens to identify novel potential therapeutic compounds.

STUDY POPULATION:

We plan to recruit 25 participants with Best disease, 25 participants with

L-ORD, 50 participants with AMD and 75 healthy volunteers without any retinal disease. If possible, unaffected siblings and relatives of patients will be included as healthy volunteers.

DESIGN:

In this basic science, research-oriented study, skin, hair and blood samples will be collected from participants with Best disease, L-ORD and AMD and from control participants matched for age, gender and ethnicity. The sample collection procedures will incur only minimal risk to participants. This study will typically require only one visit by each participant. The skin fibroblast, keratinocyte and CD34+ blood samples will then be used to generate patient-specific iPS cells and these cells will then be differentiated into RPE cells. 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 Best disease, L-ORD and AMD.

OUTCOME MEASURES:

The outcome measures for this study include the creation of iPS cells from the three types of somatic tissues collected from each patient, the differentiation of iPS cells into RPE cells and the identification of molecular and physiological phenotypes in RPE cells that may be linked to the onset or progression of Best disease, L-ORD and AMD. This analysis may lead to the discovery of therapeutic interventions for these diseases. There are no specific patient-based clinical outcomes for this protocol. Participants will be seen only once for this protocol, as they will be receiving the standard of care under the NEI Evaluation and Treatment Protocol (08-EI-0169) or other NEI protocols.

Observational
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  • Retinal Disease
  • AMD
  • Retinal Degeneration
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
375
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  • 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 the CEP290 or CRX genes.

    e. Participant has been diagnosed with Joubert syndrome, defined as the presence of retinal dysfunction and/or degeneration and mutations in the CEP290 or CC2D2A genes.

    f. Participant has been diagnosed with X-linked RP, defined as a presentation that is typical of the disease and mutations in the RPGR or RP2 genes.

    g. Participant diagnosed with oculocutaneous albinism, type 1A, defined as classic clinical presentation with at least one disease causing mutation in the tyrosinase gene.

    h. Participant diagnosed with oculocutaneous albinism, type 1B, defined as classic clinical presentation with at least one disease causing mutation in the tyrosinase gene.

    i. Participant has been diagnosed with oculocutaneous albinism, type 2, defined as classic clinical presentation with at least one disease causing mutation in the P gene.

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

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

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

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

    n. Participant is free of retinal diseases and could serve as an unaffected control. Participant s age (within five years), gender, and ethnicity must match an existing participant with Best disease, L-ORD, AMD, LCA, Joubert syndrome, or X-linked RP. 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, OCA1A, OCA1B, OCA2, Stargardt s disease, Waardenburg syndrome 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.

3. Medical history that includes any of the following, as per AABB or FDA requirements for allogeneic use:

  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

    4. Febrile (temperature > 38 (Infinite) C)

    5. Hemoglobin level

    -African American women < 11.5 grams/dL

    -Other women < 12.0 grams/dL

    -Men < 12.5 grams/dL

    6. HCT

    -African American women < 34%

    • Other women < 36%
    • Men < 38%

      7. Platelets < 150 x 103/ (Micro)L

      8. Absolute neutrophil count < 1.0 x 103/ (Micro)L

      9. 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).

Both
1 Year and older
Yes
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
United States
 
NCT01432847
110245, 11-EI-0245
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National Eye Institute (NEI)
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Principal Investigator: Brian P Brooks, M.D. National Eye Institute (NEI)
National Institutes of Health Clinical Center (CC)
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP