Impact of Sirolimus and Maraviroc on CCR5 Expression and the HIV-1 Reservoir in HIV-infected Kidney Transplant Recipients
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02990312|
Recruitment Status : Recruiting
First Posted : December 13, 2016
Last Update Posted : June 1, 2018
|Condition or disease||Intervention/treatment||Phase|
|Hiv Kidney Transplant HIV Reservoir CCR5||Drug: Sirolimus + Maraviroc||Phase 4|
The study will be a pilot, prospective, single-center, open-label, non-randomized, non-controlled clinical trial. 15 HIV-infected kidney transplant recipients will be enrolled in the study. Recruitment will be conducted through the renal transplant and infectious diseases outpatient clinics at the University of Maryland.
The study will include patients with stable glomerular filtration rates (GFRs) >25 with suppressed HIV with CD4 counts >200. These patients will be recruited from the University of Maryland's transplant nephrology and infectious diseases clinics. The transplant nephrology clinic is a multidisciplinary clinic that incorporates nephrologists, pharmacists to aid in medication management, and coordinators to assist the patients in coordination of care.
All patients will be screened either at the Institute of Human Virology (IHV) Clinical Research Unit or in the transplant nephrology or infectious disease clinics. At this visit, all patients will sign an informed consent as approved by our institutional review board (IRB), have a history and physical examination, and have screening clinical and research labs drawn. Additional requirements will be Trofile testing prior to enrollment. Eligibility will be determined based upon these results.
Study drugs will be prescribed (if the patient is not already taking them) starting on day 0 after an interval history and physical examination is performed and safety labs (and pregnancy tests for women of childbearing potential) are checked. The medications will be filled by the patient's pharmacy, using their insurance as these are both Food and Drug Administration (FDA) approved drugs.
Patients will be initially monitored weekly for sirolimus levels and renal function, until their sirolimus is at the pre-determined (by their transplant nephrologist) steady state. They will then be followed at week 4, and then every 12 weeks while they are on the new medication combination. Safety labs (blood counts, renal and liver function), HIV viral loads, cluster of differentiation 4 (CD4) counts, and rapamycin levels will be reviewed at each of these visits and if not checked within the specified time period these labs will be repeated at the study visit. Patients will also be advised about study adherence and monitored for adverse events.
Safety and adverse event monitoring will occur each study visit. Research nurses will inquire about adverse events that may or may not be related to study drugs. Any unfavorable medical occurrences will be recorded, whether or not considered related to the patient's participation in the research or temporally associated with the patient's participation in the research. Any grade 3 or 4 AEs and all serious adverse events (SAEs) will be reviewed as they occur by the study team. Adverse events (AEs) classified as grade 3 or higher occurring at a frequency greater than that expected by the study team will be reported to the IRB and principal investigator.
The end of treatment visit will occur at week 96. Clinical safety labs (blood counts, renal and liver function), HIV viral load, CD4 counts and rapamycin levels will be performed at this visit if not done in the pre-specified time period. Patients will be given the option, in conjunction with their transplant nephrologist and their infectious disease provider, to discontinue or continue the new medications at this time.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Effect of Sirolimus Plus Maraviroc on the Expression of Chemokine Receptor 5 (CCR5) and the HIV-1 Viral Reservoir in HIV-Infected Renal Transplant Recipients|
|Actual Study Start Date :||May 1, 2017|
|Estimated Primary Completion Date :||January 2020|
|Estimated Study Completion Date :||July 2020|
Experimental: Sirolimus + Maraviroc
Participants will be placed on the combination of Sirolimus and Maraviroc, unless they are already on one of these medications.
Drug: Sirolimus + Maraviroc
Patients will be placed on the combination of Sirolimus and Maraviroc starting on Day 0 and followed for 96 weeks during which they will have regular monitoring of both clinical safety labs, Sirolimus levels, and research labs to look at the HIV reservoir, CCR5 density, and immune activation
- HIV viral reservoir [ Time Frame: 96 weeks ]total cellular HIV DNA
- Secondary measures of the HIV viral reservoir [ Time Frame: 96 weeks ]Chromosomal HIV DNA
- Circulating HIV [ Time Frame: 96 weeks ]Ultrasensitive HIV RNA
- CCR5 Receptor Density [ Time Frame: 96 weeks ]CCR5 receptor density
- CCR5 Expression [ Time Frame: 96 weeks ]Percentage of T cells expressing CCR5
- Acute cellular rejection [ Time Frame: 96 weeks ]Incidence of T cell mediated rejection (ACR)
- Antibody mediated rejection [ Time Frame: 96 weeks ]Incidence of antibody mediated rejection (AMR)
- Markers of immune activation/inflammation measured by Ki67 [ Time Frame: 96 weeks ]Measurement of Ki67
- Markers of immune activation/inflammation measured by cluster of differentiation 38 (CD38) [ Time Frame: 96 weeks ]Measurement of CD38
- Markers of immune activation/inflammation measured by human leukocyte antigen-antigen D Related (HLA DR) [ Time Frame: 96 weeks ]Measurement of HLA DR
- Markers of immune activation/inflammation measured by programmed death 1 (PD-1) [ Time Frame: 96 weeks ]Measurement of PD-1
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02990312
|Contact: Jennifer S Husson, MD,MPHemail@example.com|
|Contact: Ilise Marrazzo, RN,BSN,CCRP||410-706-2564||IMarrazzo@ihv.umaryland.edu|
|United States, Maryland|
|Institute of human virology||Recruiting|
|Baltimore, Maryland, United States, 21201|
|Contact: Jennifer Husson, MD 410-706-6973 Jhusson@ihv.umaryland.edu|
|Contact: Ilise Marrazzo 4107062564 IMarrazzo@ihv.umaryland.edu|
|Principal Investigator:||Jennifer S Husson, MD,MPH||University of Maryland|