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

NCT ID: NCT02431325

Last Updated: 2023-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2021-01-21

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.

Conditions

HIV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Teduglutide

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

Group Type: EXPERIMENTAL

Teduglutide

Intervention Type: DRUG

Placebo

Placebo, subcutaneous injection, 6 months duration

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Teduglutide

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Gattex

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ragon Institute of MGH, MIT and Harvard

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Janet Lo, MD

Assistant Professor in Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Janet Lo, MD, MMSc

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R01HL123351-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2013P002669

Identifier Type: -

Identifier Source: org_study_id