Skin and Blood Research Samples From Healthy Volunteers and Patients With Hematologic Diseases

Anemia, Sickle Cell Clinical Trial

Official title:

Acquisition of Skin Biopsies and Blood Samples From Normal Volunteers and Patients With Benign, Inherited Hematologic Diseases for Research Purposes

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00840567
• Other study ID #: 08-1409
• Status: Terminated
• Phase: N/A
• First received: February 9, 2009
• Last updated: July 9, 2013
• Start date: February 2009
• Est. completion date: October 2010

Study information

• Verified date: July 2013
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

• To obtain skin biopsy samples from normal healthy volunteers and patients with a benign, inherited hematologic disease, such as sickle cell anemia, to create induced pluripotent stem cells. Pluripotency will be confirmed by injecting potential iPS cell lines into immunodeficient mice, assessing the ability of each line to cause cystic teratomas in recipient mice.

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

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

• To 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.

• To establish the genetic consequences of homologous recombination in human induced pluripotent stem cells and embryonic stem cells by genomic analysis, including whole genome sequencing.

• To obtain blood samples to confirm genetic mutations in patients with an inherited hematologic disease (and to confirm no mutations in healthy volunteers).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18.

• No active systemic skin infection at biopsy site.

• No allergy to lidocaine or other local anesthetics

Exclusion Criteria:

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Hematologic Diseases

Intervention

Procedure:
• Skin biopsy

• Blood draw & sample

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (18)

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. — View Citation

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. Epub 2007 Dec 6. — View Citation

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):346-53. doi: 10.1016/j.stem.2008.08.014. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2007 Dec 23. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2005 Dec 15. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2007 Jun 6. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Define the efficiency of homologous recombination in induced pluripotent stem cells derived from skin biopsy samples.	Only one blood draw and biopsy but analysis may take one year.	1 year	No
Secondary	Define the efficiency of homologous recombination in human embryonic stem cells using NIH-approved cell lines	Only one blood draw and biopsy but analysis may take one year.	1 year	No
Secondary	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	Only one blood draw and biopsy but analysis may take one year.	1 year	No
Secondary	Obtain blood samples to confirm genetic mutations in patients with an inherited hematologic disease	Only one blood draw but analysis may take one year.	1 year	No

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine