Human Immunodeficiency VirusNCT02218320

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

An observational study of Human Immunodeficiency Virus, run by University of North Carolina, Chapel Hill at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Human Immunodeficiency Virus
What is being tested?: Raltegravir, Dolutegravir and Colonoscopy with biopsy
Type of treatment: Surgery or procedure
How many people: 20 participants
Where: 1 siteUnited States
Study dates: Oct 2014to Oct 2015
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Study population: Subjects will be recruited from University of North Carolina Infectious Diseases Clinic.

Who may be able to join

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.

Who cannot join

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.

Show all 14Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Clinical and Translational Research Center, UNC Hospitals
Chapel Hill, North Carolina, 27599

Other trials in United States

About this study

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

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.

Read the detailed 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.

Conditions: Human Immunodeficiency Virus
Being tested: Raltegravir, Dolutegravir, Colonoscopy with biopsy
Keywords: HIV, Gut-associated lymphoid tissue, raltegravir, Isentress, dolutegravir, Tivicay, pharmacodynamics
Medical subject headings: Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RaltegravirDrug
Also called Isentress ®
DolutegravirDrug
Also called Tivicay ®
Colonoscopy with biopsyProcedure or surgery
This procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.

Study groups in NCT02218320
Study group	Role	What they receive
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. Receives: Drug: Raltegravir; Procedure: Colonoscopy with biopsy
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. Receives: Drug: Dolutegravir; Procedure: Colonoscopy with biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2014Oct 2015

First posted18 Aug 2014 (estimated)
Study startOct 2014
Primary completionOct 2015
Study completionOct 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Human Immunodeficiency VirusStudies of the same condition, open and under way.
More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Other
Time perspective: Prospective
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02218320
Sponsor's protocol ID: 14-1647
Status last verified: Apr 2017
First submitted: 13 Aug 2014
Last updated: 26 Dec 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 29714167

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Human Immunodeficiency Virus trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02218320
Acronym / sponsor ID: 14-1647
Conditions: Human Immunodeficiency Virus
Keywords: HIV, Gut-associated lymphoid tissue, raltegravir, Isentress, dolutegravir, Tivicay, pharmacodynamics
Study type: Observational
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: University of North Carolina, Chapel HillUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: Oct 2014
Primary completion: Oct 2015 (actual)
Study completion: Oct 2015 (actual)
First posted: 18 Aug 2014 (estimated)
Results: Posted 29 Oct 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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

Study design

Observational model: Other
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
Group A	–	Drug: Raltegravir, Procedure: Colonoscopy with biopsyTen 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	–	Drug: Dolutegravir, Procedure: Colonoscopy with biopsyTen 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.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Subjects will be recruited from University of North Carolina Infectious Diseases Clinic.

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (14 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RaltegravirAlso: Isentress ®	Drug	Group A
DolutegravirAlso: Tivicay ®	Drug	Group B
Colonoscopy with biopsyThis procedure is not standard of care for patients receiving combination antiretroviral therapy (cART), but is necessary to obtain tissue samples.	Procedure or surgery	Group A, Group B

Primary outcome

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

Results and safety

Results posted to the registry on 29 Oct 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group A	10	10
Group B	10	10

Primary outcome: Rectal Tissue Concentrations of Ralegravir and Dolutegravir

Time frame: 2 to 6 hours post dose. Median (Full Range). Unit: ng/g

Measure	Group A n = 10	Group B n = 10
Value	5308 (3938 to 19600)	810 (510 to 1408)

Group A vs Group B: p = 1.0, Wilcoxon (Mann-Whitney)

Primary outcome: RNA Concentrations From Gastrointestinal Tissues

Time frame: 2 to 6 hours post dose. Median (Full Range). Unit: copies/1000cells

Measure	Group A n = 10	Group B n = 10
Value	0.05 (0.03 to 0.34)	0.16 (0.01 to 36.19)

Primary outcome: Percentage of Total CD8+ T-cells With CCR5 Expression

Time frame: 2 to 6 hours post dose. Median (Full Range). Unit: percentage of total cells

Measure	Group A n = 10	Group B n = 10
Value	0.15 (0.07 to 0.52)	0.64 (0.24 to 1.60)

Adverse events

Time frame: 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).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group A	0 of 10 (0%)	3 of 10 (30%)	0 of 10
Group B	0 of 10 (0%)	3 of 10 (30%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29714167Weber 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Angela DM Kashuba, PharmD principal investigator

University of North Carolina, Chapel Hill

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Human Immunodeficiency Virus, run by University of North Carolina, Chapel Hill at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rectal Tissue Concentrations of Ralegravir and Dolutegravir (time frame: 2 to 6 hours post dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02218320, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2018.