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Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

NCTNCT02431325 (opens ClinicalTrials.gov in a new tab)Other id2013P002669Other id1R01HL123351-01

Overview

Status
Completed
Phase
Phase 2
Enrollment
32 participants (actual)
Sponsor
Massachusetts General Hospital · Other
Design
Randomized · Quadruple masking
Countries
1 country

United States

Start
Dec 2015
Primary completion
21 Jan 2020
Completion
21 Jan 2021
First posted
1 May 2015 (estimated)
Last update posted
12 Jun 2023
Conditions
HIV

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2016201820202022
  1. Ph 2

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

    NCT02431325

    Dec 2015 to 21 Jan 2021

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • TeduglutideDrug
  • PlaceboDrug

Arms2

  • Experimental

    Teduglutide

    Teduglutide, subcutaneous injection, 0.05 mg/kg/day, 6 months duration

  • Placebo comparator

    Placebo

    Placebo, subcutaneous injection, 6 months duration

Primary outcomes3

Outcomes the sponsor listed as primary.

  1. Change in Arterial Target to Background Ratio of 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Uptake

    Time frame · Change from baseline at 6 months

    Registry description

    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.

  2. Change in Intestinal Epithelial Integrity

    Time frame · Change from baseline at 6 months

    Registry description

    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.

  3. Change in Soluble CD14 Concentration

    Time frame · Change from baseline at 6 months

    Registry description

    Soluble CD14 is a marker of monocyte activation. An increase in soluble CD14 concentration indicates an increase in inflammation.

Secondary outcomes(17)
  1. Change in Intestinal CD4+ T-cells

    Time frame · Change from baseline at 6 months

    Registry description

    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.

  2. Change in CD14+CD86+CD40+ Monocytes

    Time frame · Change from baseline at 6 months

    Registry description

    Change in pro-inflammatory monocytes. A positive change indicates increased inflammation.

  3. Change in HLA-DR+CD38+ CD8+ T Cells

    Time frame · Change from baseline at 6 months

    Registry description

    Change in activated CD8+ T Cells. A positive change indicates increased inflammation.

  4. Change in HLA-DR+CD38+ CD4+ T Cells

    Time frame · Change from baseline at 6 months

    Registry description

    Change in activated CD4+ T Cells. A positive change indicates increased inflammation.

  5. Change in Soluble CD163 Concentration

    Time frame · Change from baseline at 6 months

    Registry description

    An increase in soluble CD163 concentration indicates an increase in inflammation.

  6. Change in Intestinal Fatty Acid Binding Protein Concentration

    Time frame · Change from baseline at 6 months

    Registry description

    An increase in I-FABP indicates an increase in intestinal mucosal damage.

  7. Change in Plasma Riboflavin Concentration

    Time frame · Change from baseline at 6 months

    Registry description

    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.

  8. Change in Bone Mineral Density

    Time frame · Change from baseline at 6 months

    Registry description

    Change in femoral neck bone mineral density. An increase in bone mineral density is beneficial for bone health.

  9. Change in Plaque Volume on Cardiac Computed Tomography Angiography

    Time frame · Change from baseline at 6 months

    Registry description

    Noncalcified plaque volume. Increased noncalcified plaque volume may indicate increased atherosclerosis.

  10. Change in Hemoglobin A1c Percentage

    Time frame · Change from baseline at 6 months

    Registry description

    A higher hemoglobin A1c percentage indicates a higher blood glucose level over a 3 month average.

  11. Change in Homeostatic Model Assessment-Insulin Resistance (HOMA-IR)

    Time frame · Change from baseline at 6 months

    Registry description

    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.

  12. Change in Visceral Adipose Tissue (VAT) Area

    Time frame · Change from baseline at 6 months

    Registry description

    Abdominal VAT area was measured using single-slice abdominal CT at the level of the fourth lumbar vertebra. VAT is considered metabolically unhealthy fat.

  13. Change in Subcutaneous Adipose Tissue (SAT) Area

    Time frame · Change from baseline at 6 months

    Registry description

    Abdominal SAT area was measured using single-slice abdominal CT at the level of the fourth lumbar vertebra.

  14. Change in Body Mass Index (BMI)

    Time frame · Change from baseline at 6 months

    Registry description

    BMI is a measure of adiposity.

  15. Change in Depressive Symptoms

    Time frame · Change from baseline at week 12 and at week 24

    Registry description

    Change in the Center for Epidemiological Studies-Depression (CES-D) score. Scores range from 0 to 60, with high scores indicating greater depressive symptoms.

  16. Change in Cognitive Performance, Defined as a Global Neurocognitive Z-score

    Time frame · Change from baseline at week 24

    Registry description

    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.

  17. Change in Domain-specific Cognitive Performance, Defined as a Domain-specific Neurocognitive Z-score

    Time frame · Change from baseline at week 24

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Change from baseline at 6 months

Change in Arterial Target to Background Ratio of 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Uptake

GroupValue (ratio)Spread
Teduglutide-0.280.29
Placebo0.010.35
Primary outcomeMean· Change from baseline at 6 months

Change in Intestinal Epithelial Integrity

GroupValue (log2 ratio)Spread
Teduglutide0.390.67
Placebo-0.100.22
Primary outcomeMean· Change from baseline at 6 months

Change in Soluble CD14 Concentration

GroupValue (ng/mL)Spread
Teduglutide117.70387.56
Placebo142.85242.01
Secondary and other outcome results(5)
Secondary outcomeMean· Change from baseline at 6 months

Change in Intestinal CD4+ T-cells

GroupValue (percentage of CD4+ T-cells)Spread
Teduglutide13.1718.15
Placebo-4.8115.98
Secondary outcomeMean· Change from baseline at 6 months

Change in CD14+CD86+CD40+ Monocytes

GroupValue (percentage of CD14+ monocytes)Spread
Teduglutide-19.2414.12
Placebo-3.3113.97
Secondary outcomeMean· Change from baseline at 6 months

Change in HLA-DR+CD38+ CD8+ T Cells

GroupValue (percentage of T Cells)Spread
Teduglutide-0.330.68
Placebo0.671.22
Secondary outcomeMean· Change from baseline at 6 months

Change in HLA-DR+CD38+ CD4+ T Cells

GroupValue (percentage of T Cells)Spread
Teduglutide0.00130.19
Placebo0.0580.31
Secondary outcomeMean· Change from baseline at 6 months

Change in Soluble CD163 Concentration

GroupValue (ng/mL)Spread
Teduglutide-9.26102.74
Placebo22.7785.95

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
TeduglutideTeduglutide, subcutaneous injection, 0.05 mg/kg/day, 6 months duration Teduglutide0 / 170 / 1710 / 17
PlaceboPlacebo, subcutaneous injection, 6 months duration Placebo0 / 150 / 1512 / 15

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 21 Years up to 65 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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