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

Human Immunodeficiency Virus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02218320
• Other study ID #: 14-1647
• Status: Completed
• Start date: October 2014
• Est. completion date: October 2015

Study information

• Verified date: April 2017
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a Phase IV, open label, observational 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.

Description:

Purpose: To compare virologic and immunologic responses to raltegravir and dolutegravir in the gastrointestinal tract of HIV-positive men and women

Participants: Twenty HIV-infected volunteers will be enrolled equally into two groups. Group A will consist of subjects receiving an antiretroviral regimen of raltegravir, tenofovir, and emtricitabine and Group B will consist of subjects receiving an antiretroviral regimen of dolutegravir, tenofovir, and emtricitabine.

Procedures (methods): This is a Phase IV, open label study to compare the gastrointestinal tissue concentrations, cytokine response, and viral replication in gut-associated lymphoid tissue of two integrase-inhibitors in HIV-infected volunteers who are virologically suppressed in blood plasma. Subjects will undergo an observed bowel preparation, followed by a colonoscopy in which tissue will be obtained by a board-certified gastroenterologist from the terminal ileum/ascending colon, splenic flexture, and rectum/sigmoid colon. Blood plasma will be collected immediately prior to collection of tissue samples.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus
• Immunologic Deficiency Syndromes

Intervention

Drug:
• Raltegravir

• Dolutegravir

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.

Locations

Country	Name	City	State
United States	Clinical and Translational Research Center, UNC Hospitals	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rectal Tissue Concentrations of Ralegravir and Dolutegravir		2 to 6 hours post dose
Primary	RNA Concentrations From Gastrointestinal Tissues	We measured RNA concentrations in copies/1000cells for both drug groups	2 to 6 hours post dose
Primary	Percentage of Total CD8+ T-cells With CCR5 Expression	Local immunologic markers in gastrointestinal tract tissues	2 to 6 hours post dose