HIVPhase 2LAMBCHOPNCT01839734
Lubiprostone as a Modulator of Gut Microbial Translocation in HIV With Incomplete CD4 Recovery on Antiretroviral Therapy
A Phase 2 study testing Lubiprostone in people with HIV, run by Ruth M. Rothstein CORE Center at 1 site in United States.
Trial summary
The use of lubiprostone will decrease the levels of immune activation in HIV-infected subjects with incomplete CD4+ T-cell recovery with antiretroviral therapy (ART). Lubiprostone will decrease levels of translocated gut microbial products in HIV-infected subjects with incomplete CD4+ T-cell recovery with ART. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV
- What is being tested?
- Lubiprostone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Feb 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
- On tenofovir/emtricitabine/efavirenz single tablet combination therapy for at least 72 weeks prior to study entry.
- No plans to change the antiretroviral regimen at least in the next 3 months after study entry.
- CD4+ cell count < 350 cells/mm3 obtained within 120 days prior to study entry at any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
- All previous CD4+ cell counts should be < 350 cells/mm3 for at least 72 weeks prior to study entry while subjects were on ART.
- Documentation of HIV-1 RNA below the limit of detection (e.g., < 50 copies/mL on Roche Amplicor HIV-1 Monitor assay, < 75 copies/mL on the Versant HIV-1 RNA assay by branched DNA, < 400 copies/mL on a standard Roche Amplicor assay, < 40 copies/mL on the Abbott m2000sp/m2000rt real-time PCR test, < 48 copies/mL on the COBAS AmpliPrep/TAQMAN HIV-1 assay) verified by at least two measurements prior to study entry, one of which must be at least 48 weeks prior to study entry and one measurement that was obtained between 121 days and 48 weeks prior to study entry.
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- Screening HIV-1 RNA below the limit of detection obtained within 120 days prior to study entry using a FDA -approved assay (e.g., < 50 copies/mL on Roche Amplicor HIV-1 Monitor assay, < 75 copies/mL on the Versant HIV-1 RNA assay by branched DNA, < 40 copies/mL on the Abbott m2000sp/m2000rt real-time PCR test, < 48 copies/mL on the COBAS AmpliPrep/TAQMAN HIV-1 assay).
- Fasting laboratory values obtained within 45 days prior to entry as follows:
- Absolute neutrophil count (ANC) ≥ 1000/mm3
- Hemoglobin ≥ 10.0 g/dL
- Platelet count ≥ 50,000/mm3
- International normalized ratio (INR)
- Female subjects of reproductive potential (defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months; i.e., those who have had menses within the preceding 24 months or have not undergone a sterilization procedure [hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or bilateral salpingectomy]) must have a negative serum or urine β-HCG pregnancy test with a sensitivity of at least 50 mIU/mL performed within 24 hours prior to study entry.
- If participating in sexual activity that could lead to pregnancy, the female subject must agree to use one form of contraceptive as listed below while receiving protocol-specified treatment and for 4 weeks after stopping the treatment.
- If the female subject is not of reproductive potential (girls who have not reached menarche, women who have been post-menopausal for at least 24 consecutive months, or women who have undergone surgical sterilization, e.g., hysterectomy, bilateral oophorectomy, or bilateral tubal ligation or salpingectomy), she is eligible without requiring the use of a contraceptive. Self report is acceptable documentation of sterilization, other contraceptive methods, and menopause.
- Men and women age ≥ 18 and ≤ 65 years of age.
- Ability and willingness of subject or legally authorized representative to provide informed consent.
Who cannot join
- Active diarrhea (3 or more unformed stools per day) within 28 days prior to study entry (except if site investigator or primary care provider attributes diarrhea to antiretroviral or azithromycin use).
- History of or active inflammatory bowel disease.
- History of significant liver disease, defined as having chronic liver disease (including chronic alcoholic liver disease, hepatitis B or C), plus either: a) ascites, b) encephalopathy, or c) a Child-Pugh Score of > 7.
- Receipt of antimicrobial therapy within 30 days prior to study entry.
- NOTE: Antimicrobial use for prophylaxis of opportunistic infections, e.g., azithromycin or trimethoprim-sulfamethoxazole, is allowed.
- Active infection requiring the use of antibiotics within 30 days prior to study entry.
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- Known allergy/sensitivity or any hypersensitivity to components of study drug or their formulation.
- Serious illness requiring systemic treatment and/or hospitalization within 14 days prior to entry.
- Use of any of the following medications for more than 3 consecutive days within the 60 days prior to study entry:
- Immunosuppressives (e.g., azathioprine, corticosteroids [physiologic replacement doses are allowed], cyclosporine, mycophenolate, NSAIDs (nonsteroidal anti-inflammatory drugs), sirolimus, sulfasalazine, tacrolimus)
- Immune modulators (e.g., cytokines [e.g., IL-2], granulocyte colony stimulating factor, growth hormone, tumor necrosis factor antagonists, thalidomide)
- Antineoplastic agents
- Probiotics (defined as products that contain significant amounts of live microorganisms and are ingested for specific health benefits, e.g., yogurt with live and active cultures, Lactobacillus GG, Saccharomyces boulardii)
- Anticoagulants (e.g., warfarin and heparin)
- Vaccinations within 1 week prior to the pre-entry or study entry visits.
- NOTE: Subjects are encouraged to get the flu vaccine prior to study pre-entry visit.
- Participation on any HIV immunotherapy/therapeutic vaccination trials within 6 months prior to study entry.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Breastfeeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ruth M. Rothstein CORE Center
Chicago, Illinois, 60612
About this study
Official title: LAMBCHOP-Lubiprostone Activity Among the MicroBiota of the Colon in HIV in Opposing Permeability: Pilot Study of Lubiprostone as a Modulator of Gut Microbial Translocation in HIV With Incomplete CD4 T-cell Recovery on Antiretroviral Therapy
The use of lubiprostone will decrease the levels of immune activation in HIV-infected subjects with incomplete CD4+ T-cell recovery with antiretroviral therapy (ART).
- Lubiprostone will decrease levels of translocated gut microbial products in HIV-infected subjects with incomplete CD4+ T-cell recovery with ART.
- The decrease in levels of translocated gut microbial products will be associated with a decline in the levels of immune activation in HIV-infected subjects with incomplete CD4+ T-cell recovery with ART.
Read the detailed description
Incomplete immune recovery in HIV-infected individuals is associated with impaired immune response to antigens, opportunistic infections, cardiovascular disease and malignancies, and increased mortality. Several studies have pointed to increased microbial translocation and immune activation as playing a causative role in these patients with limited CD4 recovery with antiretroviral therapy (ART). The gut mucosa of HIV-infected individuals sustains a rapid and profound depletion of gut mucosal CD4+ T-cells as early as a few days after infection. These changes lead to defects in mucosal immune and epithelial barrier function that allows the translocation of gut microbial products, such as plasma LPS (endotoxin) and bacterial 16s DNA. Plasma endotoxin and bacterial 16s DNA are elevated in HIV-infected individuals and their levels are associated with increased levels of immune activation. ART does not readily reverse the deficits in gut mucosal CD4+ T-cells. The epithelial barrier composed of tight junction complexes of the GI tract is a major defense that must be breached in order for microbial antigens and enterotoxins expressed by pathogenic bacteria to traverse from the lumen of the intestine to the lamina propria of the GI tract. Given recent data demonstrating increased complications and mortality in HIV-infected individuals despite suppressed viral replication on ART, investigators have proposed that adjunctive therapies aimed at reducing microbial translocation and/or its inflammatory consequences could improve the long-term prognosis of HIV-infected individuals. An intervention that decreases the level of translocated gut microbial products using modulators that act at the mucosal tight junction barrier is a strategy that has not been studied in HIV.
LAMBCHOP is a randomized, open-label, controlled two-arm study that will test whether 4 weeks of treatment with lubiprostone, an apical lumen ClC-2 chloride channel activator licensed for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation, reduces levels of translocated gut microbial products and markers of immune activation in HIV-infected subjects on antiretroviral therapy with incomplete CD4 recovery. Lubiprostone is a potent intestinal epithelial secretagogue that has been shown to stimulate recovery of mucosal barrier function via the restoration of tight junction protein complexes in ex vivo studies of ischemic porcine intestine. This study will take advantage of lubiprostone's known effect in vitro to significantly decrease E. coli and S. typhimurium translocation in a concentration-dependent manner and in in vivo mouse studies to promote enhanced protection against translocated pathogenic bacteria by shifting the intestinal microbiota in order to study the role of translocated gut microbial products in driving immune activation in HIV-infected subjects. Blood samples and stool specimens will be collected at several time points during the study to measure markers of cellular activation, inflammation, gut translocation, and coagulation. Safety assessments will be performed at screening, entry, and several post-entry visits. The primary objectives of the study is to determine whether there is a significant difference in levels of immune activation and gut microbiome after 4 weeks of study drug in those who received lubiprostone.
- Conditions
- HIV
- Being tested
- Lubiprostone
- Keywords
- CD4+
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LubiprostoneDrug
Also called Brand name: Amitiza
Lubiprostone 24 mcg by mouth (PO) once-daily
| Study group | Role | What they receive |
|---|---|---|
| Lubiprostone | Experimental | 4 weeks of treatment with lubiprostone 24 mcg by mouth (PO) once-daily (Interventional Group) Receives: Drug: Lubiprostone |
| No intervention | No intervention | No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Gut Microbial Translocation (iFABP)
Summary difference of participant's median iFABP MT marker change at week 4 from baseline aggregate median values
Measured: Baseline and 4 weeks
Changes in Gut Microbial Translocation (Zonulin)
Summary difference of participant's median Zonulin MT marker change at week 4 from baseline aggregate median values.
Measured: Baseline and 4 weeks
Changes in Gut Microbial Translocation (sCD14)
Summary difference of participant's median sCD14 MT marker change at week 4 from baseline aggregate median values
Measured: Baseline and 4 weeks
Changes in Gut Microbial Translocation (sCD163)
Summary difference of participant's median sCD163 MT marker change at week 4 from baseline aggregate median values
Measured: Baseline and 4 weeks
Secondary outcomes (4)
Changes in Systemic Inflammation (IL-6)
Summary difference of participant's median IL-6 inflammation marker change at week 4 from baseline aggregate median values.
Measured: Baseline and 4 weeks
Changes in Systemic Inflammation (hsCRP)
Summary difference of participant's median hsCRP inflammation marker change at week 4 from baseline aggregate median values
Measured: Baseline and 4 weeks
Changes in Peripheral CD4+
Summary difference of participant's median CD4+ change at week 4 from baseline aggregate median values
Measured: Baseline and 4 weeks
Number of Participants With Adverse Events During Study Period
Safety monitoring, defined as Grade ≥ 2 signs and symptoms, Grade ≥ 2 laboratory abnormalities, and other serious adverse events (SAEs) not otherwise specified.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2013 (estimated)
- Study startJun 2013
- Primary completionApr 2014
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIVStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ruth M. Rothstein CORE Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gregory Huhn, Ruth M. Rothstein CORE Center
- Investigators
- Gregory Huhn, MD, MPHTM, Principal investigator, Ruth M. Rothstein CORE Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01839734
- Sponsor's protocol ID
- 13-071
- Acronym
- LAMBCHOP
- Status last verified
- Aug 2023
- First submitted
- 18 Apr 2013
- Last updated
- 30 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LAMBCHOP-Lubiprostone Activity Among the MicroBiota of the Colon in HIV in Opposing Permeability: Pilot Study of Lubiprostone as a Modulator of Gut Microbial Translocation in HIV With Incomplete CD4 T-cell Recovery on Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT01839734
- Acronym / sponsor ID
- LAMBCHOP / 13-071
- Conditions
- HIV
- Keywords
- CD4+
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Ruth M. Rothstein CORE CenterUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Apr 2014 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 25 Apr 2013 (estimated)
- Results
- Posted 30 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The use of lubiprostone will decrease the levels of immune activation in HIV-infected subjects with incomplete CD4+ T-cell recovery with antiretroviral therapy (ART).
- Lubiprostone will decrease levels of translocated gut microbial products in HIV-infected subjects with incomplete CD4+ T-cell recovery with ART.
- The decrease in levels of translocated gut microbial products will be associated with a decline in the levels of immune activation in HIV-infected subjects with incomplete CD4+ T-cell recovery with ART.
Detailed description
Incomplete immune recovery in HIV-infected individuals is associated with impaired immune response to antigens, opportunistic infections, cardiovascular disease and malignancies, and increased mortality. Several studies have pointed to increased microbial translocation and immune activation as playing a causative role in these patients with limited CD4 recovery with antiretroviral therapy (ART). The gut mucosa of HIV-infected individuals sustains a rapid and profound depletion of gut mucosal CD4+ T-cells as early as a few days after infection. These changes lead to defects in mucosal immune and epithelial barrier function that allows the translocation of gut microbial products, such as plasma LPS (endotoxin) and bacterial 16s DNA. Plasma endotoxin and bacterial 16s DNA are elevated in HIV-infected individuals and their levels are associated with increased levels of immune activation. ART does not readily reverse the deficits in gut mucosal CD4+ T-cells. The epithelial barrier composed of tight junction complexes of the GI tract is a major defense that must be breached in order for microbial antigens and enterotoxins expressed by pathogenic bacteria to traverse from the lumen of the intestine to the lamina propria of the GI tract. Given recent data demonstrating increased complications and mortality in HIV-infected individuals despite suppressed viral replication on ART, investigators have proposed that adjunctive therapies aimed at reducing microbial translocation and/or its inflammatory consequences could improve the long-term prognosis of HIV-infected individuals. An intervention that decreases the level of translocated gut microbial products using modulators that act at the mucosal tight junction barrier is a strategy that has not been studied in HIV.
LAMBCHOP is a randomized, open-label, controlled two-arm study that will test whether 4 weeks of treatment with lubiprostone, an apical lumen ClC-2 chloride channel activator licensed for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation, reduces levels of translocated gut microbial products and markers of immune activation in HIV-infected subjects on antiretroviral therapy with incomplete CD4 recovery. Lubiprostone is a potent intestinal epithelial secretagogue that has been shown to stimulate recovery of mucosal barrier function via the restoration of tight junction protein complexes in ex vivo studies of ischemic porcine intestine. This study will take advantage of lubiprostone's known effect in vitro to significantly decrease E. coli and S. typhimurium translocation in a concentration-dependent manner and in in vivo mouse studies to promote enhanced protection against translocated pathogenic bacteria by shifting the intestinal microbiota in order to study the role of translocated gut microbial products in driving immune activation in HIV-infected subjects. Blood samples and stool specimens will be collected at several time points during the study to measure markers of cellular activation, inflammation, gut translocation, and coagulation. Safety assessments will be performed at screening, entry, and several post-entry visits. The primary objectives of the study is to determine whether there is a significant difference in levels of immune activation and gut microbiome after 4 weeks of study drug in those who received lubiprostone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lubiprostone | Experimental | Drug: Lubiprostone4 weeks of treatment with lubiprostone 24 mcg by mouth (PO) once-daily (Interventional Group) |
| No intervention | No intervention | –No intervention |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
- On tenofovir/emtricitabine/efavirenz single tablet combination therapy for at least 72 weeks prior to study entry.
- No plans to change the antiretroviral regimen at least in the next 3 months after study entry.
- CD4+ cell count < 350 cells/mm3 obtained within 120 days prior to study entry at any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
- All previous CD4+ cell counts should be < 350 cells/mm3 for at least 72 weeks prior to study entry while subjects were on ART.
Key exclusion criteria (19 listed)
- Active diarrhea (3 or more unformed stools per day) within 28 days prior to study entry (except if site investigator or primary care provider attributes diarrhea to antiretroviral or azithromycin use).
- History of or active inflammatory bowel disease.
- History of significant liver disease, defined as having chronic liver disease (including chronic alcoholic liver disease, hepatitis B or C), plus either: a) ascites, b) encephalopathy, or c) a Child-Pugh Score of > 7.
- Receipt of antimicrobial therapy within 30 days prior to study entry.
- NOTE: Antimicrobial use for prophylaxis of opportunistic infections, e.g., azithromycin or trimethoprim-sulfamethoxazole, is allowed.
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 |
|---|---|---|
| LubiprostoneAlso: Brand name: AmitizaLubiprostone 24 mcg by mouth (PO) once-daily | Drug | Lubiprostone |
Primary outcome
Changes in Gut Microbial Translocation (iFABP)
Time frame: Baseline and 4 weeks
Summary difference of participant's median iFABP MT marker change at week 4 from baseline aggregate median values
Changes in Gut Microbial Translocation (Zonulin)
Time frame: Baseline and 4 weeks
Summary difference of participant's median Zonulin MT marker change at week 4 from baseline aggregate median values.
Changes in Gut Microbial Translocation (sCD14)
Time frame: Baseline and 4 weeks
Summary difference of participant's median sCD14 MT marker change at week 4 from baseline aggregate median values
Changes in Gut Microbial Translocation (sCD163)
Time frame: Baseline and 4 weeks
Summary difference of participant's median sCD163 MT marker change at week 4 from baseline aggregate median values
4 secondary outcomes
Changes in Systemic Inflammation (IL-6)
Time frame: Baseline and 4 weeks
Changes in Systemic Inflammation (hsCRP)
Time frame: Baseline and 4 weeks
Changes in Peripheral CD4+
Time frame: Baseline and 4 weeks
Number of Participants With Adverse Events During Study Period
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Gregory Huhn, MD, MPHTM principal investigator
Ruth M. Rothstein CORE Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lubiprostone in people with HIV, run by Ruth M. Rothstein CORE Center 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 17 inclusion and 19 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 30 Aug 2023. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Changes in Gut Microbial Translocation (iFABP) (time frame: Baseline and 4 weeks). The study lists 4 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 30 Aug 2023.