HIV InfectionsRIFFTNCT05502653
Relationship of Inflammation and Pulmonary Function to Fungal Translocation in HIV
An observational study of HIV Infections and Inflammation, run by University of Pittsburgh at 1 site in United States.
Trial summary
The investigator will study the origin of fungal translocation in HIV, its relationship to the mycobiome, and its relationship to lung function and inflammation. Supported by the preliminary data and published studies, this project is based on the premise that circulating BDG derived from microbial translocation… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- HIV Infections, Inflammation, COPD
- How many people
- 102 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2022to 1 Nov 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 to 80 years
- All sexes
- Adult, Older adult
Study population: People living with HIV
Who may be able to join
- Age 18 to 80
- HIV positive
- Virally-suppressed on ART for at least 6 months
- subjects enrolled in Dr. Morris's HLRC Studies STUDY20020151, STUDY19080258, STUDY19060243, STUDY19070181, STUDY19070181, STUDY19050326 OR subjects being seen at the HIV/PACT clinics.
Who cannot join
- Contraindication to pulmonary function testing (i.e., abdominal or cataract surgery within 3 months, recent myocardial infarction, etc.).
- individuals with clinical or radiographic evidence of another significant pulmonary diagnosis (e.g. interstitial lung disease, active asthma)
- inflammatory bowel disease
- pregnancy
- use of antibiotics in the prior 2 weeks
- immunomodulators in the prior 6 months
- unable to perform any study procedures.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Relationship of Fungal Translocation, Inflammation, and Pulmonary Function in HIV
The investigator will study the origin of fungal translocation in HIV, its relationship to the mycobiome, and its relationship to lung function and inflammation. Supported by the preliminary data and published studies, this project is based on the premise that circulating BDG derived from microbial translocation stimulates inflammation and worsens lung function in PWH.
Chronic obstructive pulmonary disease (COPD) is a significant public health problem with few therapies that modify disease trajectory. COPD is a leading cause of mortality in the United States associated with increased morbidity and healthcare costs. Long-acting bronchodilators and inhaled corticosteroids are mainstays of therapy that control symptoms and reduce acute exacerbation frequency, but do not have a significant impact on mortality or lung function trajectory. The National Heart, Lung, and Blood Institute's COPD National Action Plan focuses on the critical need for research to characterize COPD risk factors and disease mechanisms in order to improve the understanding of causes and progression of disease. The ultimate goal is to provide precision therapy to appropriate patient subgroups to preserve health or arrest disease progression.
Microbial organisms in the gut may have a profound effect on lung disease. The role of the gut-lung axis, defined as the cross-talk between gut microbiota and the lungs, in the pathogenesis of chronic respiratory diseases is emerging as an area of interest. Perturbations of gut microbiota characterized by low microbial diversity and changes in microbiota abundance are linked to childhood asthma risk, airflow obstruction in adult asthma, and severe lung dysfunction in cystic fibrosis. Studies in animals show that both a high fiber diet that modulates gut microbiota and an abundance of beneficial bacterial strains attenuate inflammation, emphysema, and COPD development in response to cigarette smoke exposure in murine models. In humans, recent investigations show differences in the gut microbial communities between COPD patients and healthy individuals as well as shifts in the gut microbiome with acute exacerbations of COPD.
Read the detailed description
Baseline, 18 month and 36 month visits will all be the same.
URINE COLLECTION/INGESTION OF HYPOTONIC SOLUTION:
Assessment of gut epithelial barrier integrity: Gut epithelial barrier integrity will be measured by the lactulose/mannitol differential sugar absorption test. The test will be performed at the CTRC the morning of the baseline visit. After an overnight fast, participants will be asked to ingest a solution of 5 grams of lactulose and 2 grams of mannitol in 100 mL of tap water. All urine passed in the subsequent five hours will be collected. Total urine volume will be measured and then a 100 mL volume will be stored at -80 degrees Celsius for later measurement of sugar absorption.
BLOOD:
The investigator will obtain approximately 90 ml (6 tablespoons) blood samples for measurement of BDG and proteins. Blood will be processed for serum, plasma, and PBMCs. Small amount will be used for hemoglobin and carboxyhemoglobin to accurately interpret PFT data.
BREATHING TEST(PFT):
Breathing tests are routine clinical tests that measure lung function; spirometry (measures the ability to move air in and out of the lungs), lung volumes (measures the amount of air trapped in the lungs), and DLco measure carbon monoxide. In addition, subjects will be asked to inhale two puffs of albuterol, which is an inhaled medicine (bronchodilator) that may open up breathing passages, and to repeat some of the breathing tests. The breathing test will be performed by a PFT technician, member of study team.
ORAL WASH:
Oral wash samples will be collected by a member of study team. To get the best specimen possible, the investigator needs to collect cells from the inside of the cheeks and gums. Participants will be asked to rinse 10ml of a saline solution vigorously from one side of their mouth to the other, concentrating on cheek-to-cheek swishing.
SPUTUM:
Sputum samples may be collected by a PFT technician. Participants will be asked to wash out their mouth before the testing. Participants will be administered albuterol before the sputum induction unless they just completed a PFT in which case they would have already received albuterol. and then breathe in and out mists of salt water (3% - 5% saline) with a mouthpiece for 20 minutes. During this time, participants will actively cough and spit out their saliva ("spit") and sputum into two separate cups every 4 minutes during 20 minutes. The investigator will also monitor participant's peak flow every 4 minutes (by blowing out as hard and fast as they can through a mouth piece) during the procedure. If peak flow falls to less than 80% of baseline, sputum induction will be discontinued and albuterol administered. The investigator will examine participant's sputum for the presence of bacteria and viruses, number of cells, and amounts of chemicals called mediators. These samples will also be used to measure any chemical compounds, cells or genes in the participant's body that are involved in emphysema, COPD or other organ involvement associated with COPD.
STOOL:
Participants may be provided with a stool collection kit at the study visit. Instructions on collection and return of the samples will be provided to the participants.
QUESTIONNAIRES:
Questionnaires related to demographics, tobacco and other substance use, medical history, medications, exacerbations, symptoms, and quality of life. will be administered by a member of research team to all participants. These are paper and pencil questionnaires and can be completed while waiting for other testing.
MEDICAL RECORD REVIEW:
Information regarding smoking, illicit drug and other medication usage will be obtained. Information regarding pulmonary and cardiac diagnosis and procedures will be obtained. Only information pertaining to this research and potential pulmonary outcomes will be researched.
- Conditions
- HIV Infections, Inflammation, COPD
- Medical subject headings
- HIV Infections, Inflammation, Pulmonary Disease, Chronic Obstructive
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess intestinal and lung permeability with the lactulose/mannitol differential sugar absorption test
measure of BDG levels with the Fungitell assay44 in urine collected after 5 grams of lactulose and 2 grams of mannitol have been ingested
Measured: urine collection over 6 hours after ingestion of sugar solution at baseline
Assess intestinal and lung permeability with the lactulose/mannitol differential sugar absorption test
measure of BDG levels with the Fungitell assay44 in urine collected after 5 grams of lactulose and 2 grams of mannitol have been ingested
Measured: urine collection over 6 hours after ingestion of sugar solution at 18 months
Assess intestinal and lung permeability with the lactulose/mannitol differential sugar absorption test
measure of BDG levels with the Fungitell assay44 in urine collected after 5 grams of lactulose and 2 grams of mannitol have been ingested
Measured: urine collection over 6 hours after ingestion of sugar solution at 36 months
BDG levels will be assayed in undiluted plasma samples
Using the Fungitell Assay (Associates of Cape Cod, East Falmouth, MA)62,63 according to manufacturer's instructions, modified to utilize a lower standard curve, 7.8 -250 pg/mL. The Fungitell Assay is a chromogenic kinetic test that was approved by the Food and Drug Administration in 2003 for the clinical measurement of BDG with >80 pg/mL is considered a positive test.
Measured: Blood will be collected at baseline after ingestion of 5 grams of lactulose and 2 grams of mannitol.
BDG levels will be assayed in undiluted plasma samples
Using the Fungitell Assay (Associates of Cape Cod, East Falmouth, MA)62,63 according to manufacturer's instructions, modified to utilize a lower standard curve, 7.8 -250 pg/mL. The Fungitell Assay is a chromogenic kinetic test that was approved by the Food and Drug Administration in 2003 for the clinical measurement of BDG with >80 pg/mL is considered a positive test.
Measured: Blood will be collected at 18 months after ingestion of 5 grams of lactulose and 2 grams of mannitol.
BDG levels will be assayed in undiluted plasma samples
Using the Fungitell Assay (Associates of Cape Cod, East Falmouth, MA)62,63 according to manufacturer's instructions, modified to utilize a lower standard curve, 7.8 -250 pg/mL. The Fungitell Assay is a chromogenic kinetic test that was approved by the Food and Drug Administration in 2003 for the clinical measurement of BDG with >80 pg/mL is considered a positive test.
Measured: Blood will be collected at 36 months after ingestion of 5 grams of lactulose and 2 grams of mannitol.
Secondary outcomes (3)
Determine if higher circulating BDG levels predict disease progression and systemic immune cell activation in HIV COPD
Assess lung function at each visit with spirometry looking at the outcome of DLco progression over 3 years.
Measured: baseline
Determine if higher circulating BDG levels predict disease progression and systemic immune cell activation in HIV COPD
Assess lung function at each visit with spirometry looking at the outcome of DLco progression over 3 years.
Measured: at 18 months
Determine if higher circulating BDG levels predict disease progression and systemic immune cell activation in HIV COPD
Assess lung function at each visit with spirometry looking at the outcome of DLco progression over 3 years.
Measured: at 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2022
- Study start1 Sep 2022
- Primary completion1 Aug 2027 (estimated)
- Study completion1 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Ioannis Konstantinidis, University of Pittsburgh
- Investigators
- Alison J Morris, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05502653
- Sponsor's protocol ID
- STUDY22030175
- Acronym
- RIFFT
- Status last verified
- Sep 2026
- First submitted
- 3 Aug 2022
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relationship of Fungal Translocation, Inflammation, and Pulmonary Function in HIV
- ClinicalTrials.gov ID
- NCT05502653
- Acronym / sponsor ID
- RIFFT / STUDY22030175
- Conditions
- HIV Infections, Inflammation, COPD
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 102 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 1 Aug 2027 (estimated)
- Study completion
- 1 Nov 2028 (estimated)
- First posted
- 16 Aug 2022 (actual)
- 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 investigator will study the origin of fungal translocation in HIV, its relationship to the mycobiome, and its relationship to lung function and inflammation. Supported by the preliminary data and published studies, this project is based on the premise that circulating BDG derived from microbial translocation stimulates inflammation and worsens lung function in PWH.
Chronic obstructive pulmonary disease (COPD) is a significant public health problem with few therapies that modify disease trajectory. COPD is a leading cause of mortality in the United States associated with increased morbidity and healthcare costs. Long-acting bronchodilators and inhaled corticosteroids are mainstays of therapy that control symptoms and reduce acute exacerbation frequency, but do not have a significant impact on mortality or lung function trajectory. The National Heart, Lung, and Blood Institute's COPD National Action Plan focuses on the critical need for research to characterize COPD risk factors and disease mechanisms in order to improve the understanding of causes and progression of disease. The ultimate goal is to provide precision therapy to appropriate patient subgroups to preserve health or arrest disease progression.
Microbial organisms in the gut may have a profound effect on lung disease. The role of the gut-lung axis, defined as the cross-talk between gut microbiota and the lungs, in the pathogenesis of chronic respiratory diseases is emerging as an area of interest. Perturbations of gut microbiota characterized by low microbial diversity and changes in microbiota abundance are linked to childhood asthma risk, airflow obstruction in adult asthma, and severe lung dysfunction in cystic fibrosis. Studies in animals show that both a high fiber diet that modulates gut microbiota and an abundance of beneficial bacterial strains attenuate inflammation, emphysema, and COPD development in response to cigarette smoke exposure in murine models. In humans, recent investigations show differences in the gut microbial communities between COPD patients and healthy individuals as well as shifts in the gut microbiome with acute exacerbations of COPD.
Detailed description
Baseline, 18 month and 36 month visits will all be the same.
URINE COLLECTION/INGESTION OF HYPOTONIC SOLUTION:
Assessment of gut epithelial barrier integrity: Gut epithelial barrier integrity will be measured by the lactulose/mannitol differential sugar absorption test. The test will be performed at the CTRC the morning of the baseline visit. After an overnight fast, participants will be asked to ingest a solution of 5 grams of lactulose and 2 grams of mannitol in 100 mL of tap water. All urine passed in the subsequent five hours will be collected. Total urine volume will be measured and then a 100 mL volume will be stored at -80 degrees Celsius for later measurement of sugar absorption.
BLOOD:
The investigator will obtain approximately 90 ml (6 tablespoons) blood samples for measurement of BDG and proteins. Blood will be processed for serum, plasma, and PBMCs. Small amount will be used for hemoglobin and carboxyhemoglobin to accurately interpret PFT data.
BREATHING TEST(PFT):
Breathing tests are routine clinical tests that measure lung function; spirometry (measures the ability to move air in and out of the lungs), lung volumes (measures the amount of air trapped in the lungs), and DLco measure carbon monoxide. In addition, subjects will be asked to inhale two puffs of albuterol, which is an inhaled medicine (bronchodilator) that may open up breathing passages, and to repeat some of the breathing tests. The breathing test will be performed by a PFT technician, member of study team.
ORAL WASH:
Oral wash samples will be collected by a member of study team. To get the best specimen possible, the investigator needs to collect cells from the inside of the cheeks and gums. Participants will be asked to rinse 10ml of a saline solution vigorously from one side of their mouth to the other, concentrating on cheek-to-cheek swishing.
SPUTUM:
Sputum samples may be collected by a PFT technician. Participants will be asked to wash out their mouth before the testing. Participants will be administered albuterol before the sputum induction unless they just completed a PFT in which case they would have already received albuterol. and then breathe in and out mists of salt water (3% - 5% saline) with a mouthpiece for 20 minutes. During this time, participants will actively cough and spit out their saliva ("spit") and sputum into two separate cups every 4 minutes during 20 minutes. The investigator will also monitor participant's peak flow every 4 minutes (by blowing out as hard and fast as they can through a mouth piece) during the procedure. If peak flow falls to less than 80% of baseline, sputum induction will be discontinued and albuterol administered. The investigator will examine participant's sputum for the presence of bacteria and viruses, number of cells, and amounts of chemicals called mediators. These samples will also be used to measure any chemical compounds, cells or genes in the participant's body that are involved in emphysema, COPD or other organ involvement associated with COPD.
STOOL:
Participants may be provided with a stool collection kit at the study visit. Instructions on collection and return of the samples will be provided to the participants.
QUESTIONNAIRES:
Questionnaires related to demographics, tobacco and other substance use, medical history, medications, exacerbations, symptoms, and quality of life. will be administered by a member of research team to all participants. These are paper and pencil questionnaires and can be completed while waiting for other testing.
MEDICAL RECORD REVIEW:
Information regarding smoking, illicit drug and other medication usage will be obtained. Information regarding pulmonary and cardiac diagnosis and procedures will be obtained. Only information pertaining to this research and potential pulmonary outcomes will be researched.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- People living with HIV
Key inclusion criteria (4 listed)
- Age 18 to 80
- HIV positive
- Virally-suppressed on ART for at least 6 months
- subjects enrolled in Dr. Morris's HLRC Studies STUDY20020151, STUDY19080258, STUDY19060243, STUDY19070181, STUDY19070181, STUDY19050326 OR subjects being seen at the HIV/PACT clinics.
Key exclusion criteria (7 listed)
- Contraindication to pulmonary function testing (i.e., abdominal or cataract surgery within 3 months, recent myocardial infarction, etc.).
- individuals with clinical or radiographic evidence of another significant pulmonary diagnosis (e.g. interstitial lung disease, active asthma)
- inflammatory bowel disease
- pregnancy
- use of antibiotics in the prior 2 weeks
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
Assess intestinal and lung permeability with the lactulose/mannitol differential sugar absorption test
Time frame: urine collection over 6 hours after ingestion of sugar solution at baseline
measure of BDG levels with the Fungitell assay44 in urine collected after 5 grams of lactulose and 2 grams of mannitol have been ingested
Assess intestinal and lung permeability with the lactulose/mannitol differential sugar absorption test
Time frame: urine collection over 6 hours after ingestion of sugar solution at 18 months
measure of BDG levels with the Fungitell assay44 in urine collected after 5 grams of lactulose and 2 grams of mannitol have been ingested
Assess intestinal and lung permeability with the lactulose/mannitol differential sugar absorption test
Time frame: urine collection over 6 hours after ingestion of sugar solution at 36 months
measure of BDG levels with the Fungitell assay44 in urine collected after 5 grams of lactulose and 2 grams of mannitol have been ingested
BDG levels will be assayed in undiluted plasma samples
Time frame: Blood will be collected at baseline after ingestion of 5 grams of lactulose and 2 grams of mannitol.
Using the Fungitell Assay (Associates of Cape Cod, East Falmouth, MA)62,63 according to manufacturer's instructions, modified to utilize a lower standard curve, 7.8 -250 pg/mL. The Fungitell Assay is a chromogenic kinetic test that was approved by the Food and Drug Administration in 2003 for the clinical measurement of BDG with >80 pg/mL is considered a positive test.
BDG levels will be assayed in undiluted plasma samples
Time frame: Blood will be collected at 18 months after ingestion of 5 grams of lactulose and 2 grams of mannitol.
Using the Fungitell Assay (Associates of Cape Cod, East Falmouth, MA)62,63 according to manufacturer's instructions, modified to utilize a lower standard curve, 7.8 -250 pg/mL. The Fungitell Assay is a chromogenic kinetic test that was approved by the Food and Drug Administration in 2003 for the clinical measurement of BDG with >80 pg/mL is considered a positive test.
BDG levels will be assayed in undiluted plasma samples
Time frame: Blood will be collected at 36 months after ingestion of 5 grams of lactulose and 2 grams of mannitol.
Using the Fungitell Assay (Associates of Cape Cod, East Falmouth, MA)62,63 according to manufacturer's instructions, modified to utilize a lower standard curve, 7.8 -250 pg/mL. The Fungitell Assay is a chromogenic kinetic test that was approved by the Food and Drug Administration in 2003 for the clinical measurement of BDG with >80 pg/mL is considered a positive test.
3 secondary outcomes
Determine if higher circulating BDG levels predict disease progression and systemic immune cell activation in HIV COPD
Time frame: baseline
Determine if higher circulating BDG levels predict disease progression and systemic immune cell activation in HIV COPD
Time frame: at 18 months
Determine if higher circulating BDG levels predict disease progression and systemic immune cell activation in HIV COPD
Time frame: at 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2026.
- Individual participant dataSharing planned: No
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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.
Alison J Morris, MD principal investigator
University of Pittsburgh
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 HIV Infections and Inflammation, run by University of Pittsburgh 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 4 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 8 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
Assess intestinal and lung permeability with the lactulose/mannitol differential sugar absorption test (time frame: urine collection over 6 hours after ingestion of sugar solution at baseline). The study lists 6 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 8 Sep 2026.