A Study of the Gut Barrier and Blood Vessel Inflammation in Individuals With and Without HIV
Condition: HIV
MeSH terms: Inflammation
Intervention: Teduglutide; Placebo
Intervention MeSH terms: Teduglutide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 32.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: HIV; Atherosclerosis; Microbial Translocation; Teduglutide; Gastrointestinal Permeability; Inflammation

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.
    

Eligibility criteria:

        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