HIV
Conditions
Keywords
HIV, Atherosclerosis, Microbial Translocation, Teduglutide, Gastrointestinal Permeability, Inflammation
Brief summary
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.
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.
Interventions
DRUGTeduglutide
DRUGPlacebo
Sponsors
Ragon Institute of MGH, MIT and Harvard
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Arterial Target to Background Ratio of 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Uptake | 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 in Intestinal Epithelial Integrity | 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 in Soluble CD14 Concentration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in HLA-DR+CD38+ CD4+ T Cells | Change from baseline at 6 months | Change in activated CD4+ T Cells. A positive change indicates increased inflammation. |
| Change in Soluble CD163 Concentration | Change from baseline at 6 months | An increase in soluble CD163 concentration indicates an increase in inflammation. |
| Change in Intestinal Fatty Acid Binding Protein Concentration | Change from baseline at 6 months | An increase in I-FABP indicates an increase in intestinal mucosal damage. |
| Change in Plasma Riboflavin Concentration | 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 in Bone Mineral Density | 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 in Plaque Volume on Cardiac Computed Tomography Angiography | Change from baseline at 6 months | Noncalcified plaque volume. Increased noncalcified plaque volume may indicate increased atherosclerosis. |
| Change in Hemoglobin A1c Percentage | Change from baseline at 6 months | A higher hemoglobin A1c percentage indicates a higher blood glucose level over a 3 month average. |
| Change in Intestinal CD4+ T-cells | 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 in Visceral Adipose Tissue (VAT) Area | 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 in Subcutaneous Adipose Tissue (SAT) Area | 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 in Body Mass Index (BMI) | Change from baseline at 6 months | BMI is a measure of adiposity. |
| Change in Depressive Symptoms | 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 in Cognitive Performance, Defined as a Global Neurocognitive Z-score | 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 in Domain-specific Cognitive Performance, Defined as a Domain-specific Neurocognitive Z-score | 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 in Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) | 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 in CD14+CD86+CD40+ Monocytes | Change from baseline at 6 months | Change in pro-inflammatory monocytes. A positive change indicates increased inflammation. |
| Change in HLA-DR+CD38+ CD8+ T Cells | Change from baseline at 6 months | Change in activated CD8+ T Cells. A positive change indicates increased inflammation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Teduglutide Teduglutide, subcutaneous injection, 0.05 mg/kg/day, 6 months duration
Teduglutide | 17 |
| Placebo Placebo, subcutaneous injection, 6 months duration
Placebo | 15 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Declined to take study medication | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Placebo shortage | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
| Overall Study | Withdrew before starting study medication | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Teduglutide |
|---|---|---|---|
| Active Smoker | 6 Participants | 11 Participants | 5 Participants |
| Age, Continuous | 54.6 years | 56.1 years | 58.3 years |
| Body mass index (BMI) | 28.6 kg/m^2 STANDARD_DEVIATION 4.4 | 27.8 kg/m^2 STANDARD_DEVIATION 4.7 | 27.1 kg/m^2 STANDARD_DEVIATION 5 |
| CD4+ T-cell count | 685 cells/mm^3 STANDARD_DEVIATION 225 | 660 cells/mm^3 STANDARD_DEVIATION 193 | 639 cells/mm^3 STANDARD_DEVIATION 165 |
| Current antiretroviral therapy (ART) use | 15 Participants | 32 Participants | 17 Participants |
| Current integrase strand transfer inhibitor (INSTI) use | 9 Participants | 22 Participants | 13 Participants |
| Current non-nucleoside reverse transcriptase inhibitors (NNRTIs) use | 5 Participants | 8 Participants | 3 Participants |
| Current protease inhibitor (PI) use | 4 Participants | 8 Participants | 4 Participants |
| Current statin use | 4 Participants | 11 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 27 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HbA1c | 5.6 HbA1c, % STANDARD_DEVIATION 0.3 | 5.6 HbA1c, % STANDARD_DEVIATION 0.3 | 5.5 HbA1c, % STANDARD_DEVIATION 0.4 |
| High density lipoprotein (HDL) cholesterol | 48.33 mg/dL STANDARD_DEVIATION 17.54 | 49.72 mg/dL STANDARD_DEVIATION 16.79 | 50.94 mg/dL STANDARD_DEVIATION 16.54 |
| Low density lipoprotein (LDL) cholesterol | 113.93 mg/dL STANDARD_DEVIATION 33.28 | 107.88 mg/dL STANDARD_DEVIATION 30.6 | 102.53 mg/dL STANDARD_DEVIATION 27.93 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 11 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 17 Participants | 11 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 12 Participants | 25 Participants | 13 Participants |
| Total cholesterol | 186.33 mg/dL STANDARD_DEVIATION 35.04 | 183.41 mg/dL STANDARD_DEVIATION 33.42 | 180.82 mg/dL STANDARD_DEVIATION 32.78 |
| Triglycerides | 120.47 mg/dL STANDARD_DEVIATION 42.93 | 129.03 mg/dL STANDARD_DEVIATION 49.76 | 136.59 mg/dL STANDARD_DEVIATION 55.28 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 15 |
| other Total, other adverse events | 10 / 17 | 12 / 15 |
| serious Total, serious adverse events | 0 / 17 | 0 / 15 |
Outcome results
Primary
Change in Arterial Target to Background Ratio of 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Uptake
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.
Time frame: Change from baseline at 6 months
Population: The subset of participants with interpretable FDG-PET scans at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Arterial Target to Background Ratio of 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Uptake | -0.28 ratio | Standard Deviation 0.29 |
| Placebo | Change in Arterial Target to Background Ratio of 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Uptake | 0.01 ratio | Standard Deviation 0.35 |
p-value: 0.01ANCOVA
Primary
Change in Intestinal Epithelial Integrity
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.
Time frame: Change from baseline at 6 months
Population: The subset of participants with available metabolite assessments at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Intestinal Epithelial Integrity | 0.39 log2 ratio | Standard Deviation 0.67 |
| Placebo | Change in Intestinal Epithelial Integrity | -0.10 log2 ratio | Standard Deviation 0.22 |
p-value: 0.04t-test, 2 sided
Primary
Change in Soluble CD14 Concentration
Soluble CD14 is a marker of monocyte activation. An increase in soluble CD14 concentration indicates an increase in inflammation.
Time frame: Change from baseline at 6 months
Population: The subset of participants with soluble CD14 available at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Soluble CD14 Concentration | 117.70 ng/mL | Standard Deviation 387.56 |
| Placebo | Change in Soluble CD14 Concentration | 142.85 ng/mL | Standard Deviation 242.01 |
p-value: 0.87t-test, 2 sided
Secondary
Change in Body Mass Index (BMI)
BMI is a measure of adiposity.
Time frame: Change from baseline at 6 months
Population: The subset of participants with heights and weights measured at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Body Mass Index (BMI) | -0.33 kg/m^2 | Standard Deviation 0.94 |
| Placebo | Change in Body Mass Index (BMI) | -0.27 kg/m^2 | Standard Deviation 1.14 |
p-value: 0.93t-test, 2 sided
Secondary
Change in Bone Mineral Density
Change in femoral neck bone mineral density. An increase in bone mineral density is beneficial for bone health.
Time frame: Change from baseline at 6 months
Population: The subset of participants with bone density scans at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Bone Mineral Density | 0.015 g/cm^2 | Standard Deviation 0.021 |
| Placebo | Change in Bone Mineral Density | -0.0078 g/cm^2 | Standard Deviation 0.022 |
p-value: 0.07t-test, 2 sided
Secondary
Change in CD14+CD86+CD40+ Monocytes
Change in pro-inflammatory monocytes. A positive change indicates increased inflammation.
Time frame: Change from baseline at 6 months
Population: The subset of participants with peripheral blood flow cytometry data available at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention. Two participants in the placebo group did not have interpretable data for this monocyte population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in CD14+CD86+CD40+ Monocytes | -19.24 percentage of CD14+ monocytes | Standard Deviation 14.12 |
| Placebo | Change in CD14+CD86+CD40+ Monocytes | -3.31 percentage of CD14+ monocytes | Standard Deviation 13.97 |
p-value: <0.05t-test, 2 sided
Secondary
Change in Cognitive Performance, Defined as a Global Neurocognitive Z-score
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.
Time frame: Change from baseline at week 24
Population: The subset of participants with neurocognitive testing results at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Cognitive Performance, Defined as a Global Neurocognitive Z-score | 0.23 z-score | Standard Deviation 0.39 |
| Placebo | Change in Cognitive Performance, Defined as a Global Neurocognitive Z-score | -0.04 z-score | Standard Deviation 0.85 |
p-value: 0.51t-test, 2 sided
Secondary
Change in Depressive Symptoms
Change in the Center for Epidemiological Studies-Depression (CES-D) score. Scores range from 0 to 60, with high scores indicating greater depressive symptoms.
Time frame: Change from baseline at week 12 and at week 24
Population: The subset of participants with complete depression scales obtained by self-administered survey at baseline, 12 weeks, and 24 weeks, excluding one participant in the placebo group that discontinued ART during the intervention. Some participants that had depression scales at 24 weeks did not have them available at 12 weeks.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teduglutide | Change in Depressive Symptoms | Change from baseline at week 24 | 1 CES-D score |
| Teduglutide | Change in Depressive Symptoms | Change from baseline at week 12 | 0 CES-D score |
| Placebo | Change in Depressive Symptoms | Change from baseline at week 24 | -3 CES-D score |
| Placebo | Change in Depressive Symptoms | Change from baseline at week 12 | 3 CES-D score |
Comparison: Change from baseline at week 24p-value: 0.09Wilcoxon (Mann-Whitney)
Comparison: Change from baseline at week 12p-value: 0.25Wilcoxon (Mann-Whitney)
Secondary
Change in Domain-specific Cognitive Performance, Defined as a Domain-specific Neurocognitive Z-score
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.
Time frame: Change from baseline at week 24
Population: The subset of participants with neurocognitive testing results at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Domain-specific Cognitive Performance, Defined as a Domain-specific Neurocognitive Z-score | 1.73 z-score | Standard Deviation 2.48 |
| Placebo | Change in Domain-specific Cognitive Performance, Defined as a Domain-specific Neurocognitive Z-score | -0.52 z-score | Standard Deviation 1.72 |
p-value: 0.07t-test, 2 sided
Secondary
Change in Hemoglobin A1c Percentage
A higher hemoglobin A1c percentage indicates a higher blood glucose level over a 3 month average.
Time frame: Change from baseline at 6 months
Population: The subset of participants with HbA1c assessed at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teduglutide | Change in Hemoglobin A1c Percentage | -0.1 HbA1c, % |
| Placebo | Change in Hemoglobin A1c Percentage | -0.1 HbA1c, % |
p-value: 0.34Wilcoxon (Mann-Whitney)
Secondary
Change in HLA-DR+CD38+ CD4+ T Cells
Change in activated CD4+ T Cells. A positive change indicates increased inflammation.
Time frame: Change from baseline at 6 months
Population: The subset of participants with peripheral blood flow cytometry at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in HLA-DR+CD38+ CD4+ T Cells | 0.0013 percentage of T Cells | Standard Deviation 0.19 |
| Placebo | Change in HLA-DR+CD38+ CD4+ T Cells | 0.058 percentage of T Cells | Standard Deviation 0.31 |
p-value: 0.68t-test, 2 sided
Secondary
Change in HLA-DR+CD38+ CD8+ T Cells
Change in activated CD8+ T Cells. A positive change indicates increased inflammation.
Time frame: Change from baseline at 6 months
Population: The subset of participants with peripheral blood flow cytometry at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in HLA-DR+CD38+ CD8+ T Cells | -0.33 percentage of T Cells | Standard Deviation 0.68 |
| Placebo | Change in HLA-DR+CD38+ CD8+ T Cells | 0.67 percentage of T Cells | Standard Deviation 1.22 |
p-value: 0.07t-test, 2 sided
Secondary
Change in Homeostatic Model Assessment-Insulin Resistance (HOMA-IR)
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.
Time frame: Change from baseline at 6 months
Population: The subset of participants with fasting glucose and fasting insulin assessed at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention and one participant in the active group that was not fasting for the study end blood draw.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) | -0.40 index | Standard Deviation 2.86 |
| Placebo | Change in Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) | 1.13 index | Standard Deviation 3.2 |
p-value: 0.33t-test, 2 sided
Secondary
Change in Intestinal CD4+ T-cells
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.
Time frame: Change from baseline at 6 months
Population: The subset of participants with available biopsy samples from endoscopies at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Intestinal CD4+ T-cells | 13.17 percentage of CD4+ T-cells | Standard Deviation 18.15 |
| Placebo | Change in Intestinal CD4+ T-cells | -4.81 percentage of CD4+ T-cells | Standard Deviation 15.98 |
p-value: 0.047t-test, 2 sided
Secondary
Change in Intestinal Fatty Acid Binding Protein Concentration
An increase in I-FABP indicates an increase in intestinal mucosal damage.
Time frame: Change from baseline at 6 months
Population: The subset of participants with I-FABP data available at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teduglutide | Change in Intestinal Fatty Acid Binding Protein Concentration | -270.04 pg/mL |
| Placebo | Change in Intestinal Fatty Acid Binding Protein Concentration | -215.27 pg/mL |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Change in Plaque Volume on Cardiac Computed Tomography Angiography
Noncalcified plaque volume. Increased noncalcified plaque volume may indicate increased atherosclerosis.
Time frame: Change from baseline at 6 months
Population: The subset of participants with available cardiac CT data at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teduglutide | Change in Plaque Volume on Cardiac Computed Tomography Angiography | -0.74 mm^3 |
| Placebo | Change in Plaque Volume on Cardiac Computed Tomography Angiography | 0.00 mm^3 |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Change in Plasma Riboflavin Concentration
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.
Time frame: Change from baseline at 6 months
Population: The subset of participants with metabolite assessments at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Plasma Riboflavin Concentration | 0.55 log2 ratio | Standard Deviation 0.77 |
| Placebo | Change in Plasma Riboflavin Concentration | -0.36 log2 ratio | Standard Deviation 0.89 |
p-value: 0.04t-test, 2 sided
Secondary
Change in Soluble CD163 Concentration
An increase in soluble CD163 concentration indicates an increase in inflammation.
Time frame: Change from baseline at 6 months
Population: The subset of participants with soluble CD163 data available at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Soluble CD163 Concentration | -9.26 ng/mL | Standard Deviation 102.74 |
| Placebo | Change in Soluble CD163 Concentration | 22.77 ng/mL | Standard Deviation 85.95 |
p-value: 0.49t-test, 2 sided
Secondary
Change in Subcutaneous Adipose Tissue (SAT) Area
Abdominal SAT area was measured using single-slice abdominal CT at the level of the fourth lumbar vertebra.
Time frame: Change from baseline at 6 months
Population: The subset of participants with single-slice abdominal CT scans performed at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Subcutaneous Adipose Tissue (SAT) Area | -9.71 cm^2 | Standard Deviation 39.91 |
| Placebo | Change in Subcutaneous Adipose Tissue (SAT) Area | -0.11 cm^2 | Standard Deviation 17.6 |
p-value: 0.51t-test, 2 sided
Secondary
Change in Visceral Adipose Tissue (VAT) Area
Abdominal VAT area was measured using single-slice abdominal CT at the level of the fourth lumbar vertebra. VAT is considered metabolically unhealthy fat.
Time frame: Change from baseline at 6 months
Population: The subset of participants with single-slice abdominal CT scans performed at baseline and study end, excluding one participant in the placebo group that discontinued ART during the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change in Visceral Adipose Tissue (VAT) Area | -12.09 cm^2 | Standard Deviation 46.59 |
| Placebo | Change in Visceral Adipose Tissue (VAT) Area | -7.94 cm^2 | Standard Deviation 32.72 |
p-value: 0.84t-test, 2 sided