Graft vs Host DiseaseNCT02398708
Comparison of Gut Microbiota, Inflammation and Symptoms Following Allogeneic HSCT
An observational study of Graft vs Host Disease and Graft Versus Host Disease, run by University of Florida at 1 site in United States.
Trial summary
The purpose of this study is to examine the gut bacteria, levels of peripheral blood inflammation markers, and symptoms in patients with and without chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplant (allo-HSCT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft vs Host Disease, Graft Versus Host Disease, Hematopoietic Stem Cell Transplantation
- What is being tested?
- Questionnaires, Blood Sample and Stool Sample
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- May 2015to Apr 2016
- 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
Study population: 20 allo-Hematopoietic Stem Cell Transplantation (HSCT) recipients with chronic graft-versus-host disease (cGVHD) and 20 allo-Hematopoietic Stem Cell Transplantation (HSCT) recipients without chronic graft-versus-host disease (cGVHD)
Who may be able to join
- Group 1: Adults (> 18 years of age) within 3 months to 3 years of receiving allogeneic hematopoietic stem cell transplant (allo-HSCT) diagnosed with cGVHD;
- Group 2: Adults (> 18 years of age) within 3 months to 3 years of receiving allo-HSCT without a diagnosis of cGVHD; and
- All participants must be able and willing to complete paper and pencil questionnaires, provide a blood and stool sample, and be able to give informed consent.
Who cannot join
- Diagnosed with a significant secondary inflammatory disease such as multiple sclerosis, Crohn's disease, rheumatoid arthritis or secondary cancer;
- History of a major psychological disorder requiring psychotropic medications or initiation of antidepressants within 30 days of enrollment;
- Incarcerated or pregnant; or
- Any other condition that in the opinion of the principal investigator (PI) may compromise study participation will not be eligible for participation in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
UF Health Cancer Hospital
Gainesville, Florida, 32608
About this study
Official title: Comparison of the Fecal Microbiome, Peripheral Inflammatory Markers, and Symptoms in Individuals Discordant for GVHD After Allogeneic Hematopoietic Stem Cell Transplant
The purpose of this study is to examine the gut bacteria, levels of peripheral blood inflammation markers, and symptoms in patients with and without chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplant (allo-HSCT). The hypothesis is that individuals with cGVHD will have lower levels of microbial diversity, higher levels of inflammatory metabolites in stool and peripheral measures, and higher levels of symptoms than individuals without cGVHD.
Read the detailed description
This study will recruit 40 (20 with cGVHD and 20 without cGVHD) adults from the Bone Marrow Transplant Program at University of Florida Health Shands Cancer Hospital. After signing informed consent, participants will fill out questionnaires and have a blood sample collected from a vein in the arm. Participants will be given a stool collection kit with instruction and will return the sample via the mail. Data will be collected and securely stored in a system used by the cancer center for research. Descriptive statistics will be used to report individual, clinical factors, and symptoms.
Knowledge gained from this study will provide preliminary data for future longitudinal studies to examine biological pathways for the development, severity and/or duration of cGVHD and symptom outcomes in individuals following allo-HSCT impacting quality of life.
- Conditions
- Graft vs Host Disease, Graft Versus Host Disease, Hematopoietic Stem Cell Transplantation, Peripheral Blood Stem Cell Transplantation
- Being tested
- Questionnaires, Blood Sample, Stool Sample, Clinical data
- Keywords
- Hematopoietic Stem Cell Transplantation, Graft versus Host Disease
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QuestionnairesOther
Both groups will have questionnaires collected and compared.
Blood SampleOther
Both groups will have a blood sample collected and compared.
Stool SampleOther
Both groups will have a stool sample collected and compared.
Clinical dataOther
Both groups will have clinical data collected and compared.
| Study group | Role | What they receive |
|---|---|---|
| Chronic Graft-Versus-Host Disease | This group will have questionnaires, clinical data, a blood sample and a stool sample collected to be compared with the other group. Receives: Other: Questionnaires; Other: Blood Sample; Other: Stool Sample; Other: Clinical data | |
| No Chronic Graft-Versus-Host Disease | This group will have questionnaires, clinical data, a blood sample and a stool sample collected to be compared with the other group. Receives: Other: Questionnaires; Other: Blood Sample; Other: Stool Sample; Other: Clinical data |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma levels of inflammatory markers (cytokines and CRP) of individuals post allogeneic HSCT
Cytokines will be analyzed using a multiplex assay by Millipore Company. Compared to the traditional enzyme-linked immunosorbant assays (ELISA), the multiplex is comparable and more sensitive to lower concentration levels of cytokines than the ELISA. One laser identifies a specific bead and another laser identifies the reported antibody associated with the bead-bound cytokine. One hundred beads for each of the 17 cytokines in every sample are assayed and a mean cytokine binding for the sample is determined. The manufacturer reports that the assay accurately measures cytokine values in a range of 1-2500pg/ml. Serum CRP will be measured using the ALPCO's (American Laboratory Products Company) high-sensitivity CRP assay which uses latex particle enhanced immunoturbidimetry for quantitative CRP determination.
Measured: Day 1
Diversity and levels of fecal microbes of individuals post allogeneic HSCT
Fecal microbial DNA will be extracted from between 50-200 mg of fecal material. The 16S ribosomal gene (V4 region) of each sample will be amplified using a barcoding system to allow multiplexing with the Illumina MiSeq system. We will use UNIFRAC algorithm to evaluate the null hypothesis that the structure of the microbial community is insensitive to cGVHD and symptoms of cGVHD. Differences in taxa are implicated by our high throughput sequencing methods will be confirmed by other techniques including culturing (where appropriate) and qPCR with taxa-specific primers.
Measured: Day 1
Behavioral responses (symptoms) of individuals post allogeneic HSCT
Measured: Day 1
Secondary outcomes (8)
Health Promoting Lifestyle Profile II (HPLPII)
The Health Promoting Lifestyle Profile II (HPLPII) will be used to identify lifestyle choices that may affect relationships and differences between groups. HPLPII measures health promoting behaviors across several dimensions with subscales of health responsibility, physical activity, nutrition, spiritual growth, interpersonal relations and stress management. This is a 52-item summated behavior rating scale using a 4-point response format to measure the frequency of self-reported health-promoting behaviors. It is a well validated toll and takes approximately 10 minutes to complete.
Measured: Day 1
Perceived Stress Scale (PSS)
The Perceived Stress Scale (PSS) will be used to measure individual's level of perceived stress which may affect levels of inflammation. This is a short 10 question form rating individuals ability to tolerate change and unpredictable situations. This is the most widely used measure of individual's perceived stress and is well validated. It takes approximately 5 minutes to complete.
Measured: Day 1
Brief Pain Inventory (BPI)
Pain will be assessed using the Brief Pain Inventory (BPI). The BPI was created to evaluate two dimensions of pain: 1) the severity and 2) the interference. This tool is well validated with Cronbach's alpha .80-.87 pain severity and .89-.92 for interference.22 The BPI consists of a body diagram to indicate location of pain and a general question asking if pain is present. Four items assess pain intensity or severity and seven item s assess pain interference. Both use an eleven point scale ranging from 0 (no pain or interference) to 10 (worst pain or interference). This instrument takes approximate five minutes to complete.
Measured: Day 1
Hospital Anxiety and Depression Scale (HADS)
Depressive symptoms will be assessed using the subscale for depression from the Hospital Anxiety and Depression Scale (HADS). 23This instrument is used to assess the presence and severity of anxiety and depressive symptoms over a seven day period. The depression subscale is comprised of seven items using a four point scale ranging from 0 (least severe) to 3 (most severe). Cronbach's alpha has been found to be high (.82-.90) for the HADS depression subscale.
Measured: Day 1
Brief Fatigue Inventory (BFI)
Fatigue will be assessed using the Brief Fatigue Inventory (BFI). The BFI is a nine item, eleven point scale that assesses physical, affective, cognitive and social domains in a two dimensions, fatigue intensity and interference. Severity scores are as follows: 1) mild (1-3), 2) moderate (4-6) and 3) severe (7-10). This tool is well establish and validated. The Cronbach's alpha ranged from .95-.96 for individual items and an internal consistency of .96 overall. The questionnaire takes approximately five minutes to complete and a global score can be ascertained by averaging the total score.
Measured: Day 1
Lee Symptom Bother Scale
The Lee Symptom Bother Scale is a multi-symptom scale that measures the severity of symptoms as described as how much a symptom bothers the patient. 25There are seven domains assessed: 1) skin, 2) eye, 3) mouth, 4) lung function, 5) nutrition, 6) psychosocial status, and 7) energy. All areas are rated using a 5 point Likert type scale where 0 indicates "Not at all" and 4 indicates "Extremely" bothered. A summary score is created by taking the mean of all items and linearly transforming that value to a 0-100 scale. The Chronbach's α is between .79 and .90. The test-retest reliability for all subscales is .74-.93 except psychosocial is .55 and lung is .28. The scale has good convergent validity.
Measured: Day 1
Memorial Symptom Assessment Scale (MSAS-SF)
To comprehensively explore symptoms, the Memorial Symptom Assessment Scale (MSAS-SF) will be used to measure multiple dimensions (frequency, severity, and distress) of 32 common cancer symptoms. The Cronbach alpha for the MSAS-SF subscales ranged from .76-.86 and the test-retest correlation coefficients ranged from .86-.94 at one day and one week respectively. The total time to complete this form is approximately 10 minutes. This form allows for patients to identify and quantify "other" symptoms.
Measured: Day 1
Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT)
Health related quality of life (HRQOL) will be measured using the Functional Assessment of Cancer Therapy- Bone Marrow Transplantation (FACT-BMT). This is a well validated HRQOL measure. This is a 27-item questionnaire asking questions across four domains: physical well-being, social well-being, emotional well-being and functional well-being. This measure takes about 10 minutes to complete.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2015 (estimated)
- Study startMay 2015
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft vs Host DiseaseStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- American Cancer Society, Inc.
- Responsible party
- Sponsor
- Investigators
- Debra Lynch Kelly, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02398708
- Sponsor's protocol ID
- IRB201400992
- Other IDs
- UF-BMT-cGVHD-101, ID00023244, OCR14208
- Status last verified
- Jan 2019
- First submitted
- 20 Mar 2015
- Last updated
- 25 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Fecal Microbiome, Peripheral Inflammatory Markers, and Symptoms in Individuals Discordant for GVHD After Allogeneic Hematopoietic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT02398708
- Acronym / sponsor ID
- IRB201400992
- Conditions
- Graft vs Host Disease, Graft Versus Host Disease, Hematopoietic Stem Cell Transplantation, Peripheral Blood Stem Cell Transplantation
- Keywords
- Hematopoietic Stem Cell Transplantation, Graft versus Host Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- American Cancer Society, Inc.
- Study start
- May 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 25 Mar 2015 (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.
The purpose of this study is to examine the gut bacteria, levels of peripheral blood inflammation markers, and symptoms in patients with and without chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplant (allo-HSCT). The hypothesis is that individuals with cGVHD will have lower levels of microbial diversity, higher levels of inflammatory metabolites in stool and peripheral measures, and higher levels of symptoms than individuals without cGVHD.
Detailed description
This study will recruit 40 (20 with cGVHD and 20 without cGVHD) adults from the Bone Marrow Transplant Program at University of Florida Health Shands Cancer Hospital. After signing informed consent, participants will fill out questionnaires and have a blood sample collected from a vein in the arm. Participants will be given a stool collection kit with instruction and will return the sample via the mail. Data will be collected and securely stored in a system used by the cancer center for research. Descriptive statistics will be used to report individual, clinical factors, and symptoms.
Knowledge gained from this study will provide preliminary data for future longitudinal studies to examine biological pathways for the development, severity and/or duration of cGVHD and symptom outcomes in individuals following allo-HSCT impacting quality of life.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chronic Graft-Versus-Host Disease | – | Other: Questionnaires, Other: Blood Sample, Other: Stool Sample, Other: Clinical dataThis group will have questionnaires, clinical data, a blood sample and a stool sample collected to be compared with the other group. |
| No Chronic Graft-Versus-Host Disease | – | Other: Questionnaires, Other: Blood Sample, Other: Stool Sample, Other: Clinical dataThis group will have questionnaires, clinical data, a blood sample and a stool sample collected to be compared with the other group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 20 allo-Hematopoietic Stem Cell Transplantation (HSCT) recipients with chronic graft-versus-host disease (cGVHD) and 20 allo-Hematopoietic Stem Cell Transplantation (HSCT) recipients without chronic graft-versus-host disease (cGVHD)
Key inclusion criteria (3 listed)
- Group 1: Adults (> 18 years of age) within 3 months to 3 years of receiving allogeneic hematopoietic stem cell transplant (allo-HSCT) diagnosed with cGVHD;
- Group 2: Adults (> 18 years of age) within 3 months to 3 years of receiving allo-HSCT without a diagnosis of cGVHD; and
- All participants must be able and willing to complete paper and pencil questionnaires, provide a blood and stool sample, and be able to give informed consent.
Key exclusion criteria (4 listed)
- Diagnosed with a significant secondary inflammatory disease such as multiple sclerosis, Crohn's disease, rheumatoid arthritis or secondary cancer;
- History of a major psychological disorder requiring psychotropic medications or initiation of antidepressants within 30 days of enrollment;
- Incarcerated or pregnant; or
- Any other condition that in the opinion of the principal investigator (PI) may compromise study participation will not be eligible for participation in this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QuestionnairesBoth groups will have questionnaires collected and compared. | Other | Chronic Graft-Versus-Host Disease, No Chronic Graft-Versus-Host Disease |
| Blood SampleBoth groups will have a blood sample collected and compared. | Other | Chronic Graft-Versus-Host Disease, No Chronic Graft-Versus-Host Disease |
| Stool SampleBoth groups will have a stool sample collected and compared. | Other | Chronic Graft-Versus-Host Disease, No Chronic Graft-Versus-Host Disease |
| Clinical dataBoth groups will have clinical data collected and compared. | Other | Chronic Graft-Versus-Host Disease, No Chronic Graft-Versus-Host Disease |
Primary outcome
Plasma levels of inflammatory markers (cytokines and CRP) of individuals post allogeneic HSCT
Time frame: Day 1
Cytokines will be analyzed using a multiplex assay by Millipore Company. Compared to the traditional enzyme-linked immunosorbant assays (ELISA), the multiplex is comparable and more sensitive to lower concentration levels of cytokines than the ELISA. One laser identifies a specific bead and another laser identifies the reported antibody associated with the bead-bound cytokine. One hundred beads for each of the 17 cytokines in every sample are assayed and a mean cytokine binding for the sample is determined. The manufacturer reports that the assay accurately measures cytokine values in a range of 1-2500pg/ml. Serum CRP will be measured using the ALPCO's (American Laboratory Products Company) high-sensitivity CRP assay which uses latex particle enhanced immunoturbidimetry for quantitative CRP determination.
Diversity and levels of fecal microbes of individuals post allogeneic HSCT
Time frame: Day 1
Fecal microbial DNA will be extracted from between 50-200 mg of fecal material. The 16S ribosomal gene (V4 region) of each sample will be amplified using a barcoding system to allow multiplexing with the Illumina MiSeq system. We will use UNIFRAC algorithm to evaluate the null hypothesis that the structure of the microbial community is insensitive to cGVHD and symptoms of cGVHD. Differences in taxa are implicated by our high throughput sequencing methods will be confirmed by other techniques including culturing (where appropriate) and qPCR with taxa-specific primers.
Behavioral responses (symptoms) of individuals post allogeneic HSCT
Time frame: Day 1
8 secondary outcomes
Health Promoting Lifestyle Profile II (HPLPII)
Time frame: Day 1
Perceived Stress Scale (PSS)
Time frame: Day 1
Brief Pain Inventory (BPI)
Time frame: Day 1
Hospital Anxiety and Depression Scale (HADS)
Time frame: Day 1
Brief Fatigue Inventory (BFI)
Time frame: Day 1
Lee Symptom Bother Scale
Time frame: Day 1
Memorial Symptom Assessment Scale (MSAS-SF)
Time frame: Day 1
Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT)
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2019.
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Graft vs Host Disease
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.
Debra Lynch Kelly, PhD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Graft vs Host Disease and Graft Versus Host Disease, run by University of Florida at 1 site in United States.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 25 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
What does the primary outcome measure?
Plasma levels of inflammatory markers (cytokines and CRP) of individuals post allogeneic HSCT (time frame: Day 1). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Jan 2019.