Graft-Versus-Host-DiseaseNCT00723593
Natural History and Pathophysiology of Gastrointestinal Graft-versus-Host Disease
An observational study of Graft-Versus-Host-Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Trial summary
This study will determine the best location to biopsy the gastrointestinal (GI) tract for early and accurate diagnosis of GI graft-versus-host-disease (GVHD). (A biopsy is the surgical removal of a small piece of tissue for examination under the microscope.) GVHD is a life-threatening complication of stem cell… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft-Versus-Host-Disease
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 23 Jul 2008to 4 Feb 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients 18 years or older who have undergone or plan to undergo any type of allogeneic bone marrow or peripheral stem cell transplant. (This will be coordinated with all different institutes at NIH to involve patients who participate in NIH affiliated protocols.)
Who cannot join
- Patients who are under the age of 18 years.
- Patients with a platelet count less than 30,000/mm(3).
- Patients with an elevated prothrombin or partial thromboplastin time more than 1.5 times greater than the upper limit of normal or an absolute neutrophil count less than 500/mm(3) of blood or a history of a bleeding diathesis.
- Women who are pregnant, as determined by laboratory evaluation performed according to the referring transplant protocol, or breast feeding.
- Patients who are unable to provide informed consent.
About this study
Official title: Natural History and Pathophysiology of Gastrointestinal Graft Versus Host Disease
This study will determine the best location to biopsy the gastrointestinal (GI) tract for early and accurate diagnosis of GI graft-versus-host-disease (GVHD). (A biopsy is the surgical removal of a small piece of tissue for examination under the microscope.) GVHD is a life-threatening complication of stem cell transplantation in which the donor s immune cells destroy the patient s healthy tissues. It most commonly affects the skin, liver and GI tract. This study will establish where to best biopsy tissue from the GI tract and study the tissue to try to explore how GI GVD occurs and how it may be possible to better diagnose and treat it.
Patients 18 years of age and older who have undergone or are who will undergo stem cell transplantation and who are at high risk for developing GI GVHD may be eligible for this study. Participants may enter the study before the transplant procedure or later if they develop GVHD symptoms.
Read more
Participants undergo the following tests and procedures:
- Before starting conditioning chemotherapy or radiation therapy for the transplantation
- Medical history and physical examination
- Sigmoidoscopy (endoscopy of the lower part of the large intestine) and biopsies
- Blood draw
- Stool sample collection
II. Two to 3 weeks after conditioning regimen
- Sigmoidoscopy with biopsies
- Blood draw
- Stool sample collection
III. 30, 45, 60 and 90 days after transplantation
-Blood draw
IV. After completing the tests in part II and at the appearance of GI symptoms suspected to be due to GVHD
- Updated medical history and physical examination
- Esophagogastroduodenoscopy (endoscopy of the esophagus, stomach and upper small intestine)
- Colonoscopy (endoscopy of the entire part of the large intestine) with biopsies
- Blood draw
- Stool collection
- Two weeks after starting therapy in patients diagnosed with GVHD
- Sigmoidoscopy with biopsies
- Blood draw
- Stool sample collection
- PET/CT scan in selected patients (nuclear medicine and x-ray imaging of the GI tract
Read the detailed description
Graft-versus-host disease (GVHD) affects up to 70% of patients who undergo stem cell transplantation. GVHD is associated with significant morbidity and mortality, and commonly affects the skin, liver, and gastrointestinal (GI) system. Gastrointestinal (GI) manifestations of GVHD include anorexia, nausea, vomiting, abdominal pain, and diarrhea. In patients with GI GVHD, the extent of gut involvement and its relationship to underlying symptoms is unclear. Furthermore, diagnosis requires histologic evaluation that entails cumbersome invasive endoscopic procedures for tissue procurement. Histologic findings that support this diagnosis are nonspecific and have poor sensitivity and specificity. Treatment of GI GVHD is also nonspecific, and has many systemic side effects that account for a large portion of associated morbidity and mortality.
Such uncertainties regarding the diagnosis and treatment of GI GVHD stem from a lack of understanding of the pathophysiology of the disease. Cytokines produced by T lymphocytes, mononuclear phagocytes, and natural killer cells have been shown to play an integral role in the regulation of tissue damage. Human studies performed to date have examined peripheral blood cytokines, but results have been conflicting and with little clinical correlation. Current analysis of gut tissue has been limited mostly to animal subjects with little correlation to humans.
The primary objective of this study is to identify areas of the GI tract to be biopsied that would achieve the highest yield for the diagnosis of GI GVHD. This will be accomplished by performing esophagogastroduodenoscopy, colonoscopy, and ileoscopy in all post transplant patients with GI symptoms, suspected to be due to GVHD. Endoscopic biopsies will be evaluated by a single designated GI pathologist to make the diagnosis of GVHD. A novel application of a quantitative histological apoptotic assay will be evaluated in a blinded fashion for its diagnostic utility. A GVHD diagnostic yield rate for each area of the GI tract will be the primary outcome measure.
Other biopsies obtained at baseline, following the conditioning regimen as well as before and after therapy for GI GVHD will be used to achieve the secondary objective of understanding the immune response underlying GI GVHD. A comprehensive evaluation of the inflammatory milieu of gut tissues will be achieved using immunohistochemistry and flow cytometric immunophenotyping of mucosal mononuclear cells and microarray, qRT-PCR and ELISA of mucosal cytokines. Other secondary objectives include the evaluation of serum proteomic pattern analysis, serum citrulline, fecal calprotectin and 18F-FDG PET/CT for the noninvasive diagnosis of GI GVHD.
Better understanding of the pathophysiology of GI GVHD will allow us to develop more focused and effective diagnostic and therapeutic options that are less invasive and have fewer systemic side effects leading to reduced morbidity and mortality.
- Conditions
- Graft-Versus-Host-Disease
- Keywords
- Graft-Versus-Host Disease, Gastrointestinal, Apoptotic Assay, Serum Proteomic Pattern Analysis, Mucosal Biopsy, Graft Versus Host Disease, GVHD
- Medical subject headings
- Graft vs Host Disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2008 (estimated)
- Study start23 Jul 2008
- Study completion4 Feb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Graft-Versus-Host-DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Stephen A Wank, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00723593
- Sponsor's protocol ID
- 080187
- Other IDs
- 08-DK-0187
- Status last verified
- 4 Feb 2013
- First submitted
- 25 Jul 2008
- Last updated
- 6 Oct 2017
- Results posted
- No
Publications
Cahn JY, Klein JP, Lee SJ, Milpied N, Blaise D, Antin JH, Leblond V, Ifrah N, Jouet JP, Loberiza F, Ringden O, Barrett AJ, Horowitz MM, Socie G; Societe Francaise de Greffe de Moelle et Therapie Cellulaire; Dana Farber Cancer Institute; International Bone Marrow Transplant Registry. Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Societe Francaise de Greffe de Moelle et Therapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective study. Blood. 2005 Aug 15;106(4):1495-500. doi: 10.1182/blood-2004-11-4557. Epub 2005 May 5.
PubMed 15878974Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.
PubMed 16338616Martin PJ, McDonald GB, Sanders JE, Anasetti C, Appelbaum FR, Deeg HJ, Nash RA, Petersdorf EW, Hansen JA, Storb R. Increasingly frequent diagnosis of acute gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2004 May;10(5):320-7. doi: 10.1016/j.bbmt.2003.12.304.
PubMed 15111931
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History and Pathophysiology of Gastrointestinal Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT00723593
- Acronym / sponsor ID
- 080187
- Conditions
- Graft-Versus-Host-Disease
- Keywords
- Graft-Versus-Host Disease, Gastrointestinal, Apoptotic Assay, Serum Proteomic Pattern Analysis, Mucosal Biopsy, Graft Versus Host Disease, GVHD
- Study type
- Observational
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 23 Jul 2008
- Study completion
- 4 Feb 2013
- First posted
- 28 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine the best location to biopsy the gastrointestinal (GI) tract for early and accurate diagnosis of GI graft-versus-host-disease (GVHD). (A biopsy is the surgical removal of a small piece of tissue for examination under the microscope.) GVHD is a life-threatening complication of stem cell transplantation in which the donor s immune cells destroy the patient s healthy tissues. It most commonly affects the skin, liver and GI tract. This study will establish where to best biopsy tissue from the GI tract and study the tissue to try to explore how GI GVD occurs and how it may be possible to better diagnose and treat it.
Patients 18 years of age and older who have undergone or are who will undergo stem cell transplantation and who are at high risk for developing GI GVHD may be eligible for this study. Participants may enter the study before the transplant procedure or later if they develop GVHD symptoms.
Participants undergo the following tests and procedures:
- Before starting conditioning chemotherapy or radiation therapy for the transplantation
- Medical history and physical examination
- Sigmoidoscopy (endoscopy of the lower part of the large intestine) and biopsies
- Blood draw
- Stool sample collection
II. Two to 3 weeks after conditioning regimen
- Sigmoidoscopy with biopsies
- Blood draw
- Stool sample collection
III. 30, 45, 60 and 90 days after transplantation
-Blood draw
IV. After completing the tests in part II and at the appearance of GI symptoms suspected to be due to GVHD
- Updated medical history and physical examination
- Esophagogastroduodenoscopy (endoscopy of the esophagus, stomach and upper small intestine)
- Colonoscopy (endoscopy of the entire part of the large intestine) with biopsies
- Blood draw
- Stool collection
- Two weeks after starting therapy in patients diagnosed with GVHD
- Sigmoidoscopy with biopsies
- Blood draw
- Stool sample collection
- PET/CT scan in selected patients (nuclear medicine and x-ray imaging of the GI tract
Detailed description
Graft-versus-host disease (GVHD) affects up to 70% of patients who undergo stem cell transplantation. GVHD is associated with significant morbidity and mortality, and commonly affects the skin, liver, and gastrointestinal (GI) system. Gastrointestinal (GI) manifestations of GVHD include anorexia, nausea, vomiting, abdominal pain, and diarrhea. In patients with GI GVHD, the extent of gut involvement and its relationship to underlying symptoms is unclear. Furthermore, diagnosis requires histologic evaluation that entails cumbersome invasive endoscopic procedures for tissue procurement. Histologic findings that support this diagnosis are nonspecific and have poor sensitivity and specificity. Treatment of GI GVHD is also nonspecific, and has many systemic side effects that account for a large portion of associated morbidity and mortality.
Such uncertainties regarding the diagnosis and treatment of GI GVHD stem from a lack of understanding of the pathophysiology of the disease. Cytokines produced by T lymphocytes, mononuclear phagocytes, and natural killer cells have been shown to play an integral role in the regulation of tissue damage. Human studies performed to date have examined peripheral blood cytokines, but results have been conflicting and with little clinical correlation. Current analysis of gut tissue has been limited mostly to animal subjects with little correlation to humans.
The primary objective of this study is to identify areas of the GI tract to be biopsied that would achieve the highest yield for the diagnosis of GI GVHD. This will be accomplished by performing esophagogastroduodenoscopy, colonoscopy, and ileoscopy in all post transplant patients with GI symptoms, suspected to be due to GVHD. Endoscopic biopsies will be evaluated by a single designated GI pathologist to make the diagnosis of GVHD. A novel application of a quantitative histological apoptotic assay will be evaluated in a blinded fashion for its diagnostic utility. A GVHD diagnostic yield rate for each area of the GI tract will be the primary outcome measure.
Other biopsies obtained at baseline, following the conditioning regimen as well as before and after therapy for GI GVHD will be used to achieve the secondary objective of understanding the immune response underlying GI GVHD. A comprehensive evaluation of the inflammatory milieu of gut tissues will be achieved using immunohistochemistry and flow cytometric immunophenotyping of mucosal mononuclear cells and microarray, qRT-PCR and ELISA of mucosal cytokines. Other secondary objectives include the evaluation of serum proteomic pattern analysis, serum citrulline, fecal calprotectin and 18F-FDG PET/CT for the noninvasive diagnosis of GI GVHD.
Better understanding of the pathophysiology of GI GVHD will allow us to develop more focused and effective diagnostic and therapeutic options that are less invasive and have fewer systemic side effects leading to reduced morbidity and mortality.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients 18 years or older who have undergone or plan to undergo any type of allogeneic bone marrow or peripheral stem cell transplant. (This will be coordinated with all different institutes at NIH to involve patients who participate in NIH affiliated protocols.)
Key exclusion criteria (5 listed)
- Patients who are under the age of 18 years.
- Patients with a platelet count less than 30,000/mm(3).
- Patients with an elevated prothrombin or partial thromboplastin time more than 1.5 times greater than the upper limit of normal or an absolute neutrophil count less than 500/mm(3) of blood or a history of a bleeding diathesis.
- Women who are pregnant, as determined by laboratory evaluation performed according to the referring transplant protocol, or breast feeding.
- Patients who are unable to provide informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2017.
- Background: PubMed 15878974Cahn JY, Klein JP, Lee SJ, Milpied N, Blaise D, Antin JH, Leblond V, Ifrah N, Jouet JP, Loberiza F, Ringden O, Barrett AJ, Horowitz MM, Socie G; Societe Francaise de Greffe de Moelle et Therapie Cellulaire; Dana Farber Cancer Institute; International Bone Marrow Transplant Registry. Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Societe Francaise de Greffe de Moelle et Therapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective study. Blood. 2005 Aug 15;106(4):1495-500. doi: 10.1182/blood-2004-11-4557. Epub 2005 May 5.
- Background: PubMed 16338616Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.
- Background: PubMed 15111931Martin PJ, McDonald GB, Sanders JE, Anasetti C, Appelbaum FR, Deeg HJ, Nash RA, Petersdorf EW, Hansen JA, Storb R. Increasingly frequent diagnosis of acute gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2004 May;10(5):320-7. doi: 10.1016/j.bbmt.2003.12.304.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen A Wank, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Questions about this trial
What is this clinical trial studying?
An observational study of Graft-Versus-Host-Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00723593, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2017.