A Study of the Gut Barrier and Blood Vessel Inflammation in Individuals With and Without HIV

May 17, 2023 updated by: Janet Lo, MD, Massachusetts General Hospital

A Study to Investigate Gastrointestinal Epithelial Integrity and Arterial Inflammation in Individuals With and Without HIV

The purpose of this research study is to determine whether teduglutide can repair a "leaky" gut, decrease inflammation, and prevent or treat plaque, a build-up of fat and other materials in the blood vessels of the heart, in people with HIV. HIV disease is linked to inflammatory changes and leakiness of the gut. These changes or conditions may increase the risk of developing heart and blood vessel disease. The investigators believe teduglutide can help repair the gut barrier in people with HIV, leading to a decrease in inflammation and plaque in the blood vessels of the heart.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

As more people with HIV gain access to combination antiretroviral therapy (cART), cardiovascular disease has become increasingly prevalent and a significant cause of mortality. Activation of the innate immune system may stimulate inflammatory mechanisms of atherosclerosis development. Loss of gastrointestinal (GI) mucosal epithelial integrity and loss of CD4+ T-lymphocytes in the intestinal lamina propria occur in HIV-infected patients and are not fully restored by cART. Translocation of microbial products from the intestinal lumen into the systemic circulation has been demonstrated to be increased in HIV-infected patients and the investigators hypothesize that it is a key driver of monocyte and macrophage activation. In turn, these pro-inflammatory monocytes and macrophages can induce atherosclerotic disease development. The purpose of the research study is to determine the effects of a glucagon-like peptide-2 analog, teduglutide, on intestinal epithelial integrity, microbial translocation across the gut lumen, markers of innate immune system activation including the monocyte transcriptome, bone, arterial inflammation, and atherosclerosis in a 6-month randomized, double-blind placebo-controlled proof of concept trial in HIV-infected individuals.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
32

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Men and women age 21-65 with previously diagnosed HIV disease
  2. Stable anti-retroviral therapy (ART) as defined by no changes in ART regimen for >6 months
  3. HIV viral load < 200 copies/mL

  4. To be eligible for colonoscopy procedure, laboratory values that meet the following criteria:

    1. Hemoglobin > 9.0 g/dL
    2. Absolute neutrophil count ≥ 1000/mm3
    3. Platelet count ≥ 100,000/mm3
    4. Prothrombin time (PT) < 1.2 x upper limit of normal (ULN)
    5. Partial thromboplastin time (PTT) < 1.5 x ULN

4. Ability and willingness to give written informed consent and to comply with study requirements

Exclusion Criteria:

  1. History of clinically significant gastrointestinal disease including but not limited to: colon cancer, intestinal obstruction, ulcerative colitis, Crohn's disease, or history of C. difficile within the past 3 months
  2. First-degree relative with history of colon cancer
  3. Active gall bladder, biliary or pancreatic disease
  4. Female subject who is pregnant, nursing or less than 8 weeks post partum.
  5. Use of any immunomodulatory agents within 30 days prior to study enrollment
  6. History of intolerance, sensitivity, allergy or anaphylaxis to benzodiazepines or other narcotics to be used during the colonoscopy or upper endoscopy procedure
  7. Contraindication to beta-blocker (including moderate to severe asthma or heart block) or nitroglycerin use as these drugs are given as part of the standard cardiac CT protocol. Previous allergic reaction to beta blocker or nitroglycerin.
  8. Patients with previous allergic reactions to iodine-containing contrast media
  9. Renal disease or creatinine >1.5 mg/dL (contrast will be administered during CT angiography of the heart)
  10. History of requiring antibiotic prophylaxis for invasive procedures
  11. History of myocardial infarction, decompensated cirrhosis, or any other condition that in the opinion of the investigator will compromise ability to participate in the study
  12. Currently taking anticoagulants including but not limited to: heparin, warfarin (Coumadin), tinzaparin (Innohep), enoxaparin (Lovenox), danaparoid (Orgaran), dalteparin (Fragmin), clopidogrel (Plavix), prophylactic aspirin, and regular NSAID use
  13. Subject taking any of the following medications: statins, systemic steroids (inhaled or nasal steroid therapy is permitted), interleukins, systemic interferons (e.g. local injection of interferon alpha for treatment of human papilloma virus is permitted), systemic chemotherapy including oral chemotherapeutic agents, methotrexate, octreotide, growth hormone, antiarrhythmics including digoxin, antiepileptics, immunosuppressants, vancomycin, rifampin, aminoglycosides, clonidine, prazosin, lithium and ritonavir-boosted lopinavir (Kaletra).
  14. Subject has had two or more endoscopy procedures (sigmoidoscopy, upper endoscopy or colonoscopy) within the past 12 months for clinical purposes or other research studies.
  15. Body weight greater than 300 lbs due to CT scanner table limitations
  16. Active illicit drug use

  17. Patients who report any significant radiation exposure over the course of the year prior to randomization. Significant exposure is defined as:

    1. More than 2 percutaneous coronary interventions (PCI) within 12 months of randomization
    2. More than 2 myocardial perfusion studies within the past 12 months
    3. More than 2 CT angiograms within the past 12 months
    4. Any subjects with history of radiation therapy

  18. Patients already scheduled or being considered for a procedure or treatment

    1. requiring significant radiation exposure (e.g., radiation therapy, PCI, or catheter
    2. ablation of arrhythmia) within 12 months of randomization
  19. History of malignancy
  20. Prior recipient of a HIV vaccine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Teduglutide
Teduglutide, subcutaneous injection, 0.05 mg/kg/day, 6 months duration
Drug: Teduglutide
Other Names:
  • Gattex
Placebo Comparator: Placebo
Placebo, subcutaneous injection, 6 months duration
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Arterial Target to Background Ratio of 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Uptake
Time Frame: Change from baseline at 6 months
Change in maximum target to background ratio (TBRmax) of the most diseased segment (MDS) of the carotid index vessel. A negative number for the change in TBR implies a reduction in activity over time, which is considered an improvement in carotid arterial inflammation. Arterial FDG Uptake provides a measure of inflammation in the artery wall. TBR is target-to-background ratio (a measure of the ratio of the activity in the vessel wall divided by the blood background). The most diseased segment is the approximately 1-cm section of the vessel with the highest activity at baseline. The results are expressed as the change in the mean value, of the TBR, from baseline to 6 months.
Change from baseline at 6 months
Change in Intestinal Epithelial Integrity
Time Frame: Change from baseline at 6 months
Change in plasma citrulline is calculated as log2 of the ratio of plasma citrulline at study end to baseline. Citrulline is a measure of functional small bowel mass, so a positive number is considered an improvement in intestinal epithelial integrity.
Change from baseline at 6 months
Change in Soluble CD14 Concentration
Time Frame: Change from baseline at 6 months
Soluble CD14 is a marker of monocyte activation. An increase in soluble CD14 concentration indicates an increase in inflammation.
Change from baseline at 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Intestinal CD4+ T-cells
Time Frame: Change from baseline at 6 months
Change in CD161+CCR6+ (Th17) cells as a percentage of CD4+ T-cells in the duodenum. An increase in Th17 cells indicates a beneficial restoration of this CD4+ T-cell population in the small intestine, which are pathologically depleted in people with HIV.
Change from baseline at 6 months
Change in CD14+CD86+CD40+ Monocytes
Time Frame: Change from baseline at 6 months
Change in pro-inflammatory monocytes. A positive change indicates increased inflammation.
Change from baseline at 6 months
Change in HLA-DR+CD38+ CD8+ T Cells
Time Frame: Change from baseline at 6 months
Change in activated CD8+ T Cells. A positive change indicates increased inflammation.
Change from baseline at 6 months
Change in HLA-DR+CD38+ CD4+ T Cells
Time Frame: Change from baseline at 6 months
Change in activated CD4+ T Cells. A positive change indicates increased inflammation.
Change from baseline at 6 months
Change in Soluble CD163 Concentration
Time Frame: Change from baseline at 6 months
An increase in soluble CD163 concentration indicates an increase in inflammation.
Change from baseline at 6 months
Change in Intestinal Fatty Acid Binding Protein Concentration
Time Frame: Change from baseline at 6 months
An increase in I-FABP indicates an increase in intestinal mucosal damage.
Change from baseline at 6 months
Change in Plasma Riboflavin Concentration
Time Frame: Change from baseline at 6 months
Change in plasma riboflavin is calculated as log2 of the ratio of plasma riboflavin at study end to baseline. A positive number indicates an increase in riboflavin levels.
Change from baseline at 6 months
Change in Bone Mineral Density
Time Frame: Change from baseline at 6 months
Change in femoral neck bone mineral density. An increase in bone mineral density is beneficial for bone health.
Change from baseline at 6 months
Change in Plaque Volume on Cardiac Computed Tomography Angiography
Time Frame: Change from baseline at 6 months
Noncalcified plaque volume. Increased noncalcified plaque volume may indicate increased atherosclerosis.
Change from baseline at 6 months
Change in Hemoglobin A1c Percentage
Time Frame: Change from baseline at 6 months
A higher hemoglobin A1c percentage indicates a higher blood glucose level over a 3 month average.
Change from baseline at 6 months
Change in Homeostatic Model Assessment-Insulin Resistance (HOMA-IR)
Time Frame: Change from baseline at 6 months
A higher HOMA-IR indicates greater insulin resistance. Values greater than 2 suggests insulin resistance. HOMA-IR was calculated using a formula based on Matthews et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-419.
Change from baseline at 6 months
Change in Visceral Adipose Tissue (VAT) Area
Time Frame: Change from baseline at 6 months
Abdominal VAT area was measured using single-slice abdominal CT at the level of the fourth lumbar vertebra. VAT is considered metabolically unhealthy fat.
Change from baseline at 6 months
Change in Subcutaneous Adipose Tissue (SAT) Area
Time Frame: Change from baseline at 6 months
Abdominal SAT area was measured using single-slice abdominal CT at the level of the fourth lumbar vertebra.
Change from baseline at 6 months
Change in Body Mass Index (BMI)
Time Frame: Change from baseline at 6 months
BMI is a measure of adiposity.
Change from baseline at 6 months
Change in Depressive Symptoms
Time Frame: Change from baseline at week 12 and at week 24
Change in the Center for Epidemiological Studies-Depression (CES-D) score. Scores range from 0 to 60, with high scores indicating greater depressive symptoms.
Change from baseline at week 12 and at week 24
Change in Cognitive Performance, Defined as a Global Neurocognitive Z-score
Time Frame: Change from baseline at week 24
The Global Neurocognitive Z-Score is calculated as an average of the z-scores from the following neurocognitive assessments: Hopkins Verbal Learning Test (HVLT) Total Recall, HVLT Delayed Recall, HVLT Retention, HVLT Recognition, Wechsler Adult Intelligence Scale (WAIS) Digit Span Forward, WAIS Digit Span Backward, WAIS Digit Span Sequence, Stroop Word, Stroop Color, Stroop Color Word, Stroop Interference, Grooved Pegboard Dominant, and Grooved Pegboard Nondominant. A z-score of 0 corresponds with the population mean, and a positive z-score indicates better neurocognitive function than the population mean. A positive change indicates an improvement in neurocognitive function, and a negative change indicates a detriment to performance over time.
Change from baseline at week 24
Change in Domain-specific Cognitive Performance, Defined as a Domain-specific Neurocognitive Z-score
Time Frame: Change from baseline at week 24
Change in motor-specific performance z-score. A z-score of 0 corresponds with the population mean, and a positive z-score indicates better motor-specific performance than the population mean. A positive change indicates an improvement in motor-specific performance, and a negative change indicates a detriment to performance over time.
Change from baseline at week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Massachusetts General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)
Ragon Institute of MGH, MIT and Harvard

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Janet Lo, MD, MMSc, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 21, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 21, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 23, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 1, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 12, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 17, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2013P002669
  • 1R01HL123351-01 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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