Comparison of Virologic and Immunologic Responses to Raltegravir and Dolutegravir in the Gastrointestinal Tract of HIV-Positive Adults

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2014 by University of North Carolina, Chapel Hill
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02218320
First received: August 13, 2014
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

This is a Phase IV, open label, study to compare the gastrointestinal tissue concentrations, inflammatory response, and viral replication of two integrase-inhibitors, raltegravir and dolutegravir, in HIV-infected volunteers who are virologically suppressed in blood plasma. The study will be comprised of 20 HIV-infected volunteers who will be enrolled equally into two groups. Group A will consist of 10 subjects receiving an antiretroviral regimen of tenofovir, emtricitabine, and raltegravir, and Group B will consist of 10 subjects receiving an antiretroviral regimen of tenofovir, emtricitabine, and dolutegravir. Participants will provide small pieces of tissue, or biopsies, which will be taken from three distinct locations of the large intestine during a colonoscopy procedure. These biopsies will be used to measure the amount of raltegravir or dolutegravir, HIV virus, and inflammatory markers present in the gastrointestinal tract.


Condition Intervention Phase
Human Immunodeficiency Virus
Drug: Raltegravir
Drug: Dolutegravir
Procedure: Colonoscopy with biopsy
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IV, Open-Label Study to Compare Virologic and Immunologic Responses to Raltegravir and Dolutegravir in the Gastrointestinal Tract of HIV-Positive Men and Women

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • HIV RNA and DNA in three gastrointestinal tract tissues (terminal ileum/ascending colon, splenic flexure, and rectum/sigmoid colon) [ Time Frame: 2 to 6 hours post dose ] [ Designated as safety issue: No ]
  • Raltegravir/Dolutegravir Drug Exposure in three gastrointestinal tract tissues (terminal ileum/ascending colon, splenic flexure, and rectum/sigmoid colon) [ Time Frame: 2 to 6 hours post dose ] [ Designated as safety issue: No ]
  • Local immunologic markers in three gastrointestinal tract tissues (terminal ileum/ascending colon, splenic flexure, and rectum/sigmoid colon) [ Time Frame: 2 to 6 hours post dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: August 2014
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group A
Ten HIV-infected adults will be in Group A and take the HIV medication raltegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.
Drug: Raltegravir
Other Name: Isentress ®
Procedure: Colonoscopy with biopsy
This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.
Experimental: Group B
Ten HIV-infected adults will be in Group B and take the HIV medication dolutegravir in combination with tenofovir and emtricitabine as their provider-prescribed antiretroviral regimen.
Drug: Dolutegravir
Other Name: Tivicay ®
Procedure: Colonoscopy with biopsy
This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Healthy HIV-positive adults aged 18-65, inclusive on the date of screening, with documentation of at least one positive HIV test. Healthy is defined as no clinically relevant abnormalities that would interfere with the interpretation of results, or pose unnecessary risk onto volunteers due to study procedures.
  • Receiving an antiretroviral regimen containing tenofovir+emtricitabine with raltegravir (Group A) or dolutegravir (Group B) for 3-6 months, with blood plasma HIV RNA < 50copies/mL for at least 4 weeks, or a 2 log decrease in baseline blood plasma HIV RNA.
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
  • Documentation of at least 80% adherence to antiretroviral regimen, through clinician or self-report, with no missed doses in the 3 days prior to the inpatient visit.
  • Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
  • Women of childbearing potential must be utilizing at least one acceptable form of birth control.

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurologic disease that would pose unnecessary risk or interfere with study results. Subjects will be excluded for any condition that would increase risk from sedation, endoscopy, or biopsy.
  • Subjects with a history of having a gastrectomy, colostomy, ileostomy, or any other clinically significant procedure altering the gastrointestinal tract, or any condition possibly affecting drug absorption.
  • Subjects with inflammatory bowel diseases (ulcerative colitis or Crohn's disease).
  • Female subjects who are currently pregnant or breastfeeding, or planning to become pregnant during the study period.
  • Subjects who are unwilling to refrain from insertion of medical/recreation devices and products into the rectum, and from receptive anal intercourse, for 72 hours before inpatient study visit and through 7 days after the last biopsy unless instructed otherwise by the investigators.
  • A positive urine drug screen.
  • Untreated rectal sexually transmitted infection at screening.
  • Treatment with an investigational drug within 2 months preceding study enrollment.
  • Participated in a gastrointestinal biopsy study in the 3 months preceding study enrollment.
  • Participants with a history of clotting or bleeding disorders.
  • Participants with a history of abnormal reaction to, or complication from, conscious sedation or anesthesia
  • Subjects who are unwilling or unable to comply with the following dietary restrictions in regard to study procedures, including a clear liquid diet during bowel preparation and a period of NPO (nil per os) prior to the colonoscopy. While confined, the total daily nutritional composition will be 50% carbohydrate, 15% protein, and 35% fat. The daily caloric intake should not exceed 3200kcal.
  • Abnormalities of the colorectal mucosa, or significant colorectal symptom(s), which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids).
  • Any other reason or condition that in the judgment of the investigators would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02218320

Contacts
Contact: Heather Prince, PA-C (919)-843-6848 heather_prince@med.unc.edu
Contact: Angela DM Kashuba, PharmD akashuba@unc.edu

Locations
United States, North Carolina
Clinical and Translational Research Center, UNC Hospitals Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Angela DM Kashuba, PharmD University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02218320     History of Changes
Other Study ID Numbers: 14-1647
Study First Received: August 13, 2014
Last Updated: August 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
HIV
Gut-associated lymphoid tissue
raltegravir
Isentress
dolutegravir
Tivicay
pharmacokinetics
pharmacodynamics

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
HIV Seropositivity
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Dolutegravir
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014