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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
| |
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Raltegravir | Drug |
|
| |
| Dolutegravir |
| Measure | Description | Time Frame |
|---|---|---|
| Rectal Tissue Concentrations of Ralegravir and Dolutegravir | 2 to 6 hours post dose | |
| RNA Concentrations From Gastrointestinal Tissues | We measured RNA concentrations in copies/1000cells for both drug groups | 2 to 6 hours post dose |
| Percentage of Total CD8+ T-cells With CCR5 Expression | Local immunologic markers in gastrointestinal tract tissues | 2 to 6 hours post dose |
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Inclusion Criteria:
Exclusion Criteria:
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Subjects will be recruited from University of North Carolina Infectious Diseases Clinic.
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| Name | Affiliation | Role |
|---|---|---|
| Angela DM Kashuba, PharmD | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical and Translational Research Center, UNC Hospitals | Chapel Hill | North Carolina | 27599 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29714167 | Derived | Weber MD, Andrews E, Prince HA, Sykes C, Rosen EP, Bay C, Shaheen NJ, Madanick RD, Dellon ES, De Paris K, Nelson JA, Gay CL, Kashuba AD. Virological and immunological responses to raltegravir and dolutegravir in the gut-associated lymphoid tissue of HIV-infected men and women. Antivir Ther. 2018;23(6):495-504. doi: 10.3851/IMP3236. |
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After informed consent, all patients underwent a screening visit to determine eligibility. This visit had to occur within the 6 weeks prior to study enrollment. Patients were enrolled into the group that matched their treatment regimen.
Recruitment began upon IRB approval. Patients were enrolled from December 2014 to October 2015, at which time data analysis ensued. Enrollment continued until 20 subjects completed all study procedures. Patients were recruited from the Infectious Disease clinics associated with the University of North Carolina at Chapel Hill.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Raltegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Drug |
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| Colonoscopy with biopsy | Procedure | This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. |
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| FG001 | 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. Dolutegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Raltegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All 10 subjects underwent a bowel prep with subsequent colonoscopy to obtain tissue samples. |
| BG001 | 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. Dolutegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All 10 subjects underwent a bowel prep with subsequent colonoscopy to obtain tissue samples. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Rectal Tissue Concentrations of Ralegravir and Dolutegravir | Posted | Median | Full Range | ng/g | 2 to 6 hours post dose |
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| Primary | RNA Concentrations From Gastrointestinal Tissues | We measured RNA concentrations in copies/1000cells for both drug groups | Posted | Median | Full Range | copies/1000cells | 2 to 6 hours post dose |
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| Primary | Percentage of Total CD8+ T-cells With CCR5 Expression | Local immunologic markers in gastrointestinal tract tissues | Posted | Median | Full Range | percentage of total cells | 2 to 6 hours post dose |
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Adverse events were collected from the time of informed consent at the screening visit (up to 42 days prior to enrollment) through study completion (Up to 14 days after last sampling).
Adverse events were assessed at all visits with a standardized IRB-approved questionnaire.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Raltegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples. All participants underwent a bowel prep with subsequent colonoscopy to obtain tissue samples. | 0 | 10 | 0 | 10 | 3 | 10 |
| EG001 | 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. Dolutegravir Colonoscopy with biopsy: This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.All participants underwent a bowel prep with subsequent colonoscopy to obtain tissue samples. | 0 | 10 | 0 | 10 | 3 | 10 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thombophlebitis | Blood and lymphatic system disorders | Systematic Assessment | Onset 26Apr15, resolution 15May15, treated with Clindamycin |
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| Hypertension | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Elevated reading of blood pressure were noted on study, beginning 04May2015. Participant referred to PCP for management. |
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| Anal Irritation | Gastrointestinal disorders | Systematic Assessment | Onset and resolution 28Jan2015. Participant used aloe wipe on anus and symptoms resolved. |
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| Abdominal gas cramps | Gastrointestinal disorders | Systematic Assessment | Onset and resolution 06Jan2015. Patient ambulated to resolution of symptoms with one dose of Tylenol. |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment | Onset 13Dec14 and resolution 18Dec14. Resolved without treatment. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Angela Kashuba | University of North Carolina at Chapel Hill | 919 966-9998 | akashuba@unc.edu |
| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000068898 | Raltegravir Potassium |
| C562325 | dolutegravir |
| D003113 | Colonoscopy |
| D001706 | Biopsy |
| ID | Term |
|---|---|
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D016099 | Endoscopy, Gastrointestinal |
| D016145 | Endoscopy, Digestive System |
| D003938 | Diagnostic Techniques, Digestive System |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D004724 | Endoscopy |
| D003949 | Diagnostic Techniques, Surgical |
| D013505 | Digestive System Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D019060 | Minimally Invasive Surgical Procedures |
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D013048 | Specimen Handling |
| D008919 | Investigative Techniques |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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