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

NCT02431325 | Completed Phase 2 Results DMC

• 2 other identifiers: 2013P0026691R01HL123351-01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV

Keywords

HIV; Atherosclerosis; Microbial Translocation; Teduglutide; Gastrointestinal Permeability; Inflammation

Outcome Measures

Primary Outcomes (3)

• 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.

  Change from baseline at 6 months

• 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.

  Change from baseline at 6 months

• Change in Soluble CD14 Concentration

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

  Change from baseline at 6 months

Secondary Outcomes (17)

• Change in Intestinal CD4+ T-cells

  Change from baseline at 6 months

• Change in CD14+CD86+CD40+ Monocytes

  Change from baseline at 6 months

• Change in HLA-DR+CD38+ CD8+ T Cells

  Change from baseline at 6 months

• Change in HLA-DR+CD38+ CD4+ T Cells

  Change from baseline at 6 months

• Change in Soluble CD163 Concentration

  Change from baseline at 6 months

Study Arms (2)

Teduglutide

EXPERIMENTAL

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

Drug: Teduglutide

Placebo

PLACEBO COMPARATOR

Placebo, subcutaneous injection, 6 months duration

Drug: Placebo

Interventions

Teduglutide DRUG

Also known as: Gattex

Teduglutide

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Platelet count ≥ 100,000/mm3
• Prothrombin time (PT) \< 1.2 x upper limit of normal (ULN)
• Partial thromboplastin time (PTT) \< 1.5 x ULN
• \. Ability and willingness to give written informed consent and to comply with study requirements

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Ragon Institute of MGH, MIT and Harvard: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Atherosclerosis; Inflammation

Interventions

teduglutide; ALX-0600

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Janet Lo, M.D., M.MSc.
• Organization: Massachusetts General Hospital

jlo@mgh.harvard.edu

617-724-3425

Study Officials

• Janet Lo, MD, MMSc

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor in Medicine

Study Record Dates

• First Submitted: February 23, 2015
• First Posted: May 1, 2015
• Study Start: December 1, 2015
• Primary Completion: January 21, 2020
• Study Completion: January 21, 2021
• Last Updated: June 12, 2023
• Results First Posted: June 12, 2023

Record last verified: 2023-05

Locations

US (1)