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HIVPhase 2NCT02431325

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

A Phase 2 study testing Teduglutide in people with HIV, run by Massachusetts General Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 to 65 years
Conditions the study is for
HIV
What is being tested?
Teduglutide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
32 participants
Where
1 siteUnited States
Study dates
Dec 2015to 21 Jan 2021
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 21 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women age 21-65 with previously diagnosed HIV disease
  • Stable anti-retroviral therapy (ART) as defined by no changes in ART regimen for >6 months
  • HIV viral load < 200 copies/mL
  • To be eligible for colonoscopy procedure, laboratory values that meet the following criteria:
  • Hemoglobin > 9.0 g/dL
  • Absolute neutrophil count ≥ 1000/mm3
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  • Platelet count ≥ 100,000/mm3
  • Prothrombin time (PT) < 1.2 x upper limit of normal (ULN)
  • Partial thromboplastin time (PTT) < 1.5 x ULN
  • 4. Ability and willingness to give written informed consent and to comply with study requirements

Who cannot join

  • 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
  • First-degree relative with history of colon cancer
  • Active gall bladder, biliary or pancreatic disease
  • Female subject who is pregnant, nursing or less than 8 weeks post partum.
  • Use of any immunomodulatory agents within 30 days prior to study enrollment
  • History of intolerance, sensitivity, allergy or anaphylaxis to benzodiazepines or other narcotics to be used during the colonoscopy or upper endoscopy procedure
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  • 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.
  • Patients with previous allergic reactions to iodine-containing contrast media
  • Renal disease or creatinine >1.5 mg/dL (contrast will be administered during CT angiography of the heart)
  • History of requiring antibiotic prophylaxis for invasive procedures
  • 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
  • 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
  • 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).
  • 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.
  • Body weight greater than 300 lbs due to CT scanner table limitations
  • Active illicit drug use
  • Patients who report any significant radiation exposure over the course of the year prior to randomization. Significant exposure is defined as:
  • More than 2 percutaneous coronary interventions (PCI) within 12 months of randomization
  • More than 2 myocardial perfusion studies within the past 12 months
  • More than 2 CT angiograms within the past 12 months
  • Any subjects with history of radiation therapy
  • Patients already scheduled or being considered for a procedure or treatment
  • requiring significant radiation exposure (e.g., radiation therapy, PCI, or catheter
  • ablation of arrhythmia) within 12 months of randomization
  • History of malignancy
  • Prior recipient of a HIV vaccine

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions
HIV
Being tested
Teduglutide, Placebo
Keywords
HIV, Atherosclerosis, Microbial Translocation, Teduglutide, Gastrointestinal Permeability, Inflammation
Medical subject headings
Atherosclerosis, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TeduglutideDrug

    Also called Gattex

  • PlaceboDrug

Study groups in NCT02431325
Study groupRoleWhat they receive
TeduglutideExperimentalTeduglutide, subcutaneous injection, 0.05 mg/kg/day, 6 months duration
Receives: Drug: Teduglutide
PlaceboPlacebo comparatorPlacebo, subcutaneous injection, 6 months duration
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Change from baseline at 6 months

  2. 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.

    Measured: Change from baseline at 6 months

  3. Change in Soluble CD14 Concentration

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

    Measured: Change from baseline at 6 months

Secondary outcomes (17)
  1. 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.

    Measured: Change from baseline at 6 months

  2. Change in CD14+CD86+CD40+ Monocytes

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

    Measured: Change from baseline at 6 months

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

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

    Measured: Change from baseline at 6 months

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

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

    Measured: Change from baseline at 6 months

  5. Change in Soluble CD163 Concentration

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

    Measured: Change from baseline at 6 months

  6. Change in Intestinal Fatty Acid Binding Protein Concentration

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

    Measured: Change from baseline at 6 months

  7. 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.

    Measured: Change from baseline at 6 months

  8. Change in Bone Mineral Density

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

    Measured: Change from baseline at 6 months

  9. Change in Plaque Volume on Cardiac Computed Tomography Angiography

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

    Measured: Change from baseline at 6 months

  10. Change in Hemoglobin A1c Percentage

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

    Measured: Change from baseline at 6 months

  11. 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.

    Measured: Change from baseline at 6 months

  12. 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.

    Measured: Change from baseline at 6 months

  13. 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.

    Measured: Change from baseline at 6 months

  14. Change in Body Mass Index (BMI)

    BMI is a measure of adiposity.

    Measured: Change from baseline at 6 months

  15. 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.

    Measured: Change from baseline at week 12 and at week 24

  16. 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.

    Measured: Change from baseline at week 24

  17. 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.

    Measured: Change from baseline at week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2015 (estimated)
  2. Study startDec 2015
  3. Primary completion21 Jan 2020
  4. Study completion21 Jan 2021

Resources

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02431325
Sponsor's protocol ID
2013P002669
Other IDs
1R01HL123351-01
Status last verified
May 2023
First submitted
23 Feb 2015
Last updated
12 Jun 2023
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Teduglutide in people with HIV, run by Massachusetts General Hospital 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 10 inclusion and 26 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 12 Jun 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. Some participants in this study may receive a placebo. 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 12 Jun 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?

Change in Arterial Target to Background Ratio of 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Uptake (time frame: Change from baseline at 6 months). The study lists 3 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 12 Jun 2023.

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