Chronic Graft-versus-Host Disease in the Oral Cavity of Patients Following Allogeneic Hematopoietic Stem Cell Transplant and Including Healthy Controls
| Status: | Recruiting |
|---|---|
| Conditions: | Orthopedic, Hematology |
| Therapuetic Areas: | Hematology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 18 - 100 |
| Updated: | 11/22/2018 |
| Start Date: | November 15, 2018 |
| End Date: | May 31, 2023 |
| Contact: | Katherine M Hall, R.N. |
| Email: | katherine.hall2@nih.gov |
| Phone: | (240) 858-2341 |
Natural History of Chronic Graft-versus-Host Disease in the Oral Cavity of Patients Following Allogeneic Hematopoietic Stem Cell Transplant and Including Healthy Controls
Background:
This study follows people who have had, or will soon have, a transplant using stem cells from
another person. This is known as an allogeneic hematopoietic stem cell transplant (HSCT).
Graft-versus-host disease (cGVHD) can happen after HSCT. cGVHD can cause mouth problems and
more serious issues. Researchers want to study changes in the mouth that might indicate
cGVHD.
Objective:
To identify cGVHD in the mouth and better understand the development, treatment, and progress
of post-transplant changes in the mouth.
Eligibility:
Adults at least 18 years old who will soon undergo HSCT or have had one in the past 3 years
Healthy adults at least 18 years old
Design:
All participants will have a screening visit and baseline visit. They will last 60-90
minutes. Over these two visits, participants will have:
Medical and dental history
Dental exam.
Questions about their eating habits and general health
Blood drawn through a needle in the arm
Vital signs taken
Pictures of their mouth and lips taken
Questions about their oral health, including about pain, sensitivity, or dryness
Saliva samples taken. Participants will spit into a sterile plastic tube.
Swabs taken of the mouth and some of the saliva, plaque, and fluid from the spaces between
teeth and gums.
Participants may also have:
A piece of skin taken (biopsy) from the inner lining of the cheeks
A piece of skin taken (biopsy) from the lower lip
Dental X-rays
Urine pregnancy test
Most participants will have at least 7 study visits over 3 years. They will meet with a
dentist and repeat baseline tests.
This study follows people who have had, or will soon have, a transplant using stem cells from
another person. This is known as an allogeneic hematopoietic stem cell transplant (HSCT).
Graft-versus-host disease (cGVHD) can happen after HSCT. cGVHD can cause mouth problems and
more serious issues. Researchers want to study changes in the mouth that might indicate
cGVHD.
Objective:
To identify cGVHD in the mouth and better understand the development, treatment, and progress
of post-transplant changes in the mouth.
Eligibility:
Adults at least 18 years old who will soon undergo HSCT or have had one in the past 3 years
Healthy adults at least 18 years old
Design:
All participants will have a screening visit and baseline visit. They will last 60-90
minutes. Over these two visits, participants will have:
Medical and dental history
Dental exam.
Questions about their eating habits and general health
Blood drawn through a needle in the arm
Vital signs taken
Pictures of their mouth and lips taken
Questions about their oral health, including about pain, sensitivity, or dryness
Saliva samples taken. Participants will spit into a sterile plastic tube.
Swabs taken of the mouth and some of the saliva, plaque, and fluid from the spaces between
teeth and gums.
Participants may also have:
A piece of skin taken (biopsy) from the inner lining of the cheeks
A piece of skin taken (biopsy) from the lower lip
Dental X-rays
Urine pregnancy test
Most participants will have at least 7 study visits over 3 years. They will meet with a
dentist and repeat baseline tests.
Background:
- Chronic graft-versus-host disease (cGVHD) is a multi-organ severe alloimmune and -
autoimmune disorder that occurs after allogeneic hematopoietic stem cell transplantation
(HSCT). It is characterized by immune dysregulation, immunodeficiency, impaired organ
function, and decreased survival.
- Manifestations of cGVHD in the oral cavity are observed in 45-85% of cGVHD patients and
include 3 components: limitation of mouth opening, oral mucosal changes (lichenoid
lesions, ulceration) and salivary gland changes.
- There is an urgent need for new tools to diagnose and treat oral cGVHD. To develop
targeted therapies and non-invasive methods for serial screening, an improved
understanding of the clinical course and underlying mechanisms of oral cGVHD are
required.
Objectives:
- Advance understanding of cGVHD pathophysiology and generate hypotheses for future cGVHD
studies by tracking the longitudinal development of cGVHD in the oral cavity and
transplant-related changes in the oral microenvironment.
- Leverage knowledge about the impact of transplant on the oral cavity to develop better
protocols for supportive dental care, to refine clinical definitions and classifications
of oral cGVHD, and to test and improve criteria and tools for clinical trials.
- Include healthy volunteer cohorts both as a direct control group for HSCT patients, and
to characterize measures of interest that were not previously defined in the normal oral
cavity.
Eligibility:
- Patients who are scheduled to undergo allogeneic HSCT at the National Institutes of
Health (NIH) or who have already undergone allogeneic HSCT at the NIH or elsewhere.
- Healthy individuals who have not undergone transplant and are willing to undergo oral
exam and sample collection will be included in a control group.
- All study subjects, including patients and healthy individuals, must be able to provide
written informed consent and be willing to return to the NIH Dental Clinic for scheduled
evaluations.
Design:
- This is a single site, observational study with four cohorts. There are 2 transplant
cohorts: the New Transplant Cohort ("Cohort NT"; approximate n=300) consists of patients
who are scheduled to undergo allogeneic HSCT (under another protocol at the NIH) and the
Prior Transplant Cohort ("Cohort PT"; approximate n=100) consists of patients who have
already undergone allogeneic HSCT. These Cohorts will have up to 8 regularly scheduled
visits across 3 years, along with a variable number of acute-episode visits.
- The other 2 Cohorts include healthy volunteers: the Healthy-controls Longitudinal (HL)
Cohort ("Cohort HL"; approximate n=20) includes subjects who will participate in up to
the full set of 8 study visits across 3 years, and the Healthy-controls Short-term (HS)
Cohort ("Cohort HS"; approximate n=80) will participate in a single baseline visit.
- Each visit will include collection of biologic samples, patient-reported data and
clinical assessments.
- Initial statistical analysis will begin with unsupervised clustering methods and simple
logistic regression to identify biomarkers important in oral cGVHD. Based upon the
results of these initial analyses, more complex multivariate statistical models will be
developed to both classify and predict onset of oral cGVHD. Given the
hypothesisgenerating nature of this study, additional prospective statistical analysis
plans will be developed in consultation with a statistician as the study progresses to
address specific scientific questions.
- Chronic graft-versus-host disease (cGVHD) is a multi-organ severe alloimmune and -
autoimmune disorder that occurs after allogeneic hematopoietic stem cell transplantation
(HSCT). It is characterized by immune dysregulation, immunodeficiency, impaired organ
function, and decreased survival.
- Manifestations of cGVHD in the oral cavity are observed in 45-85% of cGVHD patients and
include 3 components: limitation of mouth opening, oral mucosal changes (lichenoid
lesions, ulceration) and salivary gland changes.
- There is an urgent need for new tools to diagnose and treat oral cGVHD. To develop
targeted therapies and non-invasive methods for serial screening, an improved
understanding of the clinical course and underlying mechanisms of oral cGVHD are
required.
Objectives:
- Advance understanding of cGVHD pathophysiology and generate hypotheses for future cGVHD
studies by tracking the longitudinal development of cGVHD in the oral cavity and
transplant-related changes in the oral microenvironment.
- Leverage knowledge about the impact of transplant on the oral cavity to develop better
protocols for supportive dental care, to refine clinical definitions and classifications
of oral cGVHD, and to test and improve criteria and tools for clinical trials.
- Include healthy volunteer cohorts both as a direct control group for HSCT patients, and
to characterize measures of interest that were not previously defined in the normal oral
cavity.
Eligibility:
- Patients who are scheduled to undergo allogeneic HSCT at the National Institutes of
Health (NIH) or who have already undergone allogeneic HSCT at the NIH or elsewhere.
- Healthy individuals who have not undergone transplant and are willing to undergo oral
exam and sample collection will be included in a control group.
- All study subjects, including patients and healthy individuals, must be able to provide
written informed consent and be willing to return to the NIH Dental Clinic for scheduled
evaluations.
Design:
- This is a single site, observational study with four cohorts. There are 2 transplant
cohorts: the New Transplant Cohort ("Cohort NT"; approximate n=300) consists of patients
who are scheduled to undergo allogeneic HSCT (under another protocol at the NIH) and the
Prior Transplant Cohort ("Cohort PT"; approximate n=100) consists of patients who have
already undergone allogeneic HSCT. These Cohorts will have up to 8 regularly scheduled
visits across 3 years, along with a variable number of acute-episode visits.
- The other 2 Cohorts include healthy volunteers: the Healthy-controls Longitudinal (HL)
Cohort ("Cohort HL"; approximate n=20) includes subjects who will participate in up to
the full set of 8 study visits across 3 years, and the Healthy-controls Short-term (HS)
Cohort ("Cohort HS"; approximate n=80) will participate in a single baseline visit.
- Each visit will include collection of biologic samples, patient-reported data and
clinical assessments.
- Initial statistical analysis will begin with unsupervised clustering methods and simple
logistic regression to identify biomarkers important in oral cGVHD. Based upon the
results of these initial analyses, more complex multivariate statistical models will be
developed to both classify and predict onset of oral cGVHD. Given the
hypothesisgenerating nature of this study, additional prospective statistical analysis
plans will be developed in consultation with a statistician as the study progresses to
address specific scientific questions.
- INCLUSION CRITERIA:
- Subjects in Cohort NT and Cohort PT must satisfy all of the following criteria in
order to participate in the study:
- Scheduled to undergo allogeneic HSCT at the NIH (Cohort NT) or have already
undergone allogeneic HSCT at the NIH or another institution (Cohort PT) and are
within 3 years of most recent bone marrow transplant
- Willing to participate in protocol evaluations including saliva collection, oral
swab collection, and completion of patient-reported outcome (PRO) forms
- Willing to return to the NIH Dental Clinic for scheduled evaluations
- Be at least 18 years of age at screening
- Be able to understand and provide written informed consent
- Subjects in Cohort HL and Cohort HS must satisfy all of the following criteria in
order to participate in the study:
- Willing to undergo oral exam and participate in Visit 1 protocol evaluations
including saliva collection and oral swab collection
- Be at least 18 years of age at screening
- Be able to understand and provide written informed consent
- Potentially be age- and/or sex-matched with a transplant patient
- Subjects in Cohort HL must additionally be willing and able to return to the NIH
Dental Clinic for scheduled visits across 3 years and participate in evaluations
including saliva collection, oral swab collection, and completion of PRO forms
EXCLUSION CRITERIA:
- Subjects in any Cohort will be excluded if they are pregnant, as pregnancy can have a
confounding effect on the oral microbiome
- Subjects in Cohort NT may not participate in the study if, in the opinion of the NIH
transplant team, participation in the protocol would not be safe or in the subject s
best interest
- Subjects in Cohort PT. There are no additional exclusion criteria for subjects in this
cohort.
- Subjects in Cohorts HL and Cohort HS may not participate in the study if they meet
either of the following criteria:
- Have any acute oral mucosal or dental infection requiring multiple dental
appointments or specialist referral for treatment; uncontrolled chronic disease;
active systemic illness; are currently undergoing orthodontic treatment; history
of frequent opportunistic infection; autoimmune disease; immunosuppressive
medications; or prior organ, bone marrow, or peripheral blood stem cell
transplant
- Are taking medications or are on other ongoing therapies that have a known or
suspected major impact on the oral microbiome
- Subjects in Cohort HL additionally may not participate if they are planning to become
pregnant within the next 3 years
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
Phone: 800-411-1222
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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