NCT00840567

Brief Summary

The investigators plan to obtain skin and blood samples from healthy volunteers and patients with a benign, inherited hematologic disease to use for research to use homologous recombination to correct β-globin gene mutations in therapeutically useful cells, like autologous induced pluripotent stem cells from sickle cell anemia patients.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
7

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Feb 2009

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2009

Completed
8 days until next milestone

First Submitted

Initial submission to the registry

February 9, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 10, 2009

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2010

Completed
Last Updated

July 11, 2013

Status Verified

July 1, 2013

Enrollment Period

1.7 years

First QC Date

February 9, 2009

Last Update Submit

July 9, 2013

Conditions

Anemia, Sickle Cell

Keywords

Stem cells

Outcome Measures

Primary Outcomes (1)

  • Obtain skin biopsy samples from normal healthy volunteers and patients with a benign, inherited hematologic disease to created induced pluripotent stem cells

    Only one biopsy but analysis may take one year.

    1 year

Secondary Outcomes (4)

  • Define the efficiency of homologous recombination in induced pluripotent stem cells derived from skin biopsy samples.

    1 year

  • Define the efficiency of homologous recombination in human embryonic stem cells using NIH-approved cell lines

    1 year

  • Establish the genetic consequences of the derivation of human induced pluripotent cells in normal controls or patients with benign, inherited hematologic diseases, by genomic analysis, including whole genome sequencing

    1 year

  • Obtain blood samples to confirm genetic mutations in patients with an inherited hematologic disease

    1 year

Study Arms (2)

Healthy Volunteers

OTHER

To obtain a one time skin sample (4 ml skin punch biopsy) and one time blood sample (1 teaspoon)

Procedure: Skin biopsyProcedure: Blood draw & sample

Patients with benign, inherited hematologic disease

OTHER

To obtain a one time skin sample (4 ml skin punch biopsy) and one time blood sample (1 teaspoon)

Procedure: Skin biopsyProcedure: Blood draw & sample

Interventions

Skin biopsyPROCEDURE
Healthy VolunteersPatients with benign, inherited hematologic disease
Blood draw & samplePROCEDURE
Healthy VolunteersPatients with benign, inherited hematologic disease

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18.
  • No active systemic skin infection at biopsy site.
  • No allergy to lidocaine or other local anesthetics

You may not qualify if:

  • ALL PATIENTS
  • History of a bleeding disorder, easy bleeding, or bruising.
  • Inability or unwillingness to provide informed consent.
  • SICKLE CELL PATIENTS
  • Platelets ≤ 50,000
  • INR ≥ 1.5
  • Currently bing given intravenous heparin

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (18)

  • Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2008 Jan 10;451(7175):141-6. doi: 10.1038/nature06534. Epub 2007 Dec 23.

    PMID: 18157115BACKGROUND

  • Park IH, Lerou PH, Zhao R, Huo H, Daley GQ. Generation of human-induced pluripotent stem cells. Nat Protoc. 2008;3(7):1180-6. doi: 10.1038/nprot.2008.92.

    PMID: 18600223BACKGROUND

  • Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell. 2008 Sep 11;3(3):340-5. doi: 10.1016/j.stem.2008.08.003.

    PMID: 18786420BACKGROUND

  • Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007 Jul 19;448(7151):313-7. doi: 10.1038/nature05934. Epub 2007 Jun 6.

    PMID: 17554338BACKGROUND

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007 Nov 30;131(5):861-72. doi: 10.1016/j.cell.2007.11.019.

    PMID: 18035408BACKGROUND

  • Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science. 2008 Nov 7;322(5903):945-9. doi: 10.1126/science.1162494. Epub 2008 Sep 25.

    PMID: 18818365BACKGROUND

  • Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 2007 Jul 19;448(7151):318-24. doi: 10.1038/nature05944. Epub 2007 Jun 6.

    PMID: 17554336BACKGROUND

  • Brambrink T, Foreman R, Welstead GG, Lengner CJ, Wernig M, Suh H, Jaenisch R. Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell. 2008 Feb 7;2(2):151-9. doi: 10.1016/j.stem.2008.01.004.

    PMID: 18371436BACKGROUND

  • Hockemeyer D, Soldner F, Cook EG, Gao Q, Mitalipova M, Jaenisch R. A drug-inducible system for direct reprogramming of human somatic cells to pluripotency. Cell Stem Cell. 2008 Sep 11;3(3):346-353. doi: 10.1016/j.stem.2008.08.014.

    PMID: 18786421BACKGROUND

  • Wernig M, Lengner CJ, Hanna J, Lodato MA, Steine E, Foreman R, Staerk J, Markoulaki S, Jaenisch R. A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nat Biotechnol. 2008 Aug;26(8):916-24. doi: 10.1038/nbt1483. Epub 2008 Jul 1.

    PMID: 18594521BACKGROUND

  • Wernig M, Meissner A, Cassady JP, Jaenisch R. c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell. 2008 Jan 10;2(1):10-2. doi: 10.1016/j.stem.2007.12.001. Epub 2007 Dec 13. No abstract available.

    PMID: 18371415BACKGROUND

  • Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, Muhlestein W, Melton DA. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol. 2008 Nov;26(11):1269-75. doi: 10.1038/nbt.1502. Epub 2008 Oct 12.

    PMID: 18849973BACKGROUND

  • Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ. Disease-specific induced pluripotent stem cells. Cell. 2008 Sep 5;134(5):877-86. doi: 10.1016/j.cell.2008.07.041. Epub 2008 Aug 7.

    PMID: 18691744BACKGROUND

  • Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, Jaenisch R. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science. 2007 Dec 21;318(5858):1920-3. doi: 10.1126/science.1152092. Epub 2007 Dec 6.

    PMID: 18063756BACKGROUND

  • Kyba M, Perlingeiro RC, Daley GQ. HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Cell. 2002 Apr 5;109(1):29-37. doi: 10.1016/s0092-8674(02)00680-3.

    PMID: 11955444BACKGROUND

  • Wang Y, Yates F, Naveiras O, Ernst P, Daley GQ. Embryonic stem cell-derived hematopoietic stem cells. Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19081-6. doi: 10.1073/pnas.0506127102. Epub 2005 Dec 15.

    PMID: 16357205BACKGROUND

  • Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science. 2008 Nov 7;322(5903):949-53. doi: 10.1126/science.1164270. Epub 2008 Oct 9.

    PMID: 18845712BACKGROUND

  • Hotta A, Ellis J. Retroviral vector silencing during iPS cell induction: an epigenetic beacon that signals distinct pluripotent states. J Cell Biochem. 2008 Nov 1;105(4):940-8. doi: 10.1002/jcb.21912.

    PMID: 18773452BACKGROUND

Related Links

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Timothy Ley, M.D.

    Washington Univerisity School of Medicine

    STUDY CHAIR

Study Design

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

Study Record Dates

First Submitted

February 9, 2009

First Posted

February 10, 2009

Study Start

February 1, 2009

Primary Completion

October 1, 2010

Study Completion

October 1, 2010

Last Updated

July 11, 2013

Record last verified: 2013-07

Locations

US(1)