Ignite Creation Date:
2024-05-06 @ 3:48 PM
Last Modification Date:
2024-10-26 @ 1:57 PM
Study NCT ID:
NCT04760691
Status:
RECRUITING
Last Update Posted:
2024-01-12
First Post:
2021-02-15
Brief Title:
Pre-Exposure Prophylaxis PrEP- Gender Affirming Hormone Therapy GAHT Interactions in TGW
Sponsor:
Johns Hopkins University
Organization:
Johns Hopkins University
Study Overview
Official Title:
A Phase I Trial for the Evaluation of the Two-way Pharmacokinetic-pharmacodynamic PD Interaction of Gender Affirming Exogenous Estrogen With Testosterone Suppression on TDFFTC PrEP in Transgender Women TGW
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a research study to determine the best way to dose Truvada an oral medication licensed to be taken as Pre-Exposure Prophylaxis PrEP to prevent HIV infection in transgender women who are also taking feminizing hormones The duration of the study is about 4 months and involves a screening visit a baseline visit with colon biopsies and kidney function testing and several outpatient visits including 5 intensive sampling visits that last about 9 hours and involve colon biopsies kidney function testing and other blood specimen collections
After the baseline visit participants will start on PrEP daily Truvada pills and will continue on the Truvada for 5 weeks Participants will then receive either an injection of Lupron oral low-dose estradiol or oral high-dose estradiol which will be taken along with the Truvada PrEP for 1-2 weeks before returning for an intensive sampling visit
After the baseline visit participants will start on PrEP daily Truvada pills and will continue on the Truvada for 5 weeks Participants will then receive either an injection of Lupron oral low-dose estradiol or oral high-dose estradiol which will be taken along with the Truvada PrEP for 1-2 weeks before returning for an intensive sampling visit
Detailed Description:
The PrEP-GAHT Interactions in TGW protocol is a phase 1 open label study to compare the safety PK and PD of five sequential phases of PrEP administration in the presence or absence of testosterone-reducing therapies or dose-escalated estrogen therapy Each participant will undergo a Screening Visit to evaluate eligibility
Following Baseline evaluation eligible participants will receive 300 milligrams mg TDF200 mg FTC Truvada once daily for seven days using direct observation approaches to achieve steady state drug PrEP concentrations After one week of therapy participants will undergo intensive PK analysis as well as collection of colorectal biopsies for PD testing PK1 During the PK-intensive day iohexol will be administered intravenously for the empirical determination of renal function and measured glomerular filtration rate mGFR While concurrently on PrEP participants will then be intramuscularly administered depot leuprolide acetate 1125 mg Lupron Two weeks post-injection when testosterone concentrations are far below the lower limit of normal of total testosterone in men typically 200 ngdL or 2 ngmL sampling for PK PD and renal function will be performed PK2
Participants will then immediately begin low-dose oral estrogen therapy 1 mg 17β-estradiol in conjunction with PrEP for one week at which time samples will be collected for the analyses described above PK3 While still on PrEP participants will then transition to high-dose estrogen therapy 6 mg 17β-estradiol for the remainder of the study One week post-high dose estrogen therapy in the presence of PrEP pharmacologic and renal samples will be collected for analysis PK4 PrEP will then be discontinued and two weeks later samples will be collected to assess renal function and hormonal concentrations and evaluate the presence of any remaining PrEP in plasma Peripheral Blood Mononuclear Cells PBMC or colorectal tissue though it should be near undetectable levels for most analytes according to the investigators prior dataPK5
Safety assessments including historyphysical chemistryhematology labs at screening and interim history will be performed at each study-intensive visit Additionally periodic assessments of gender dysphoria will be conducted at baseline and a convenient time during PK visits throughout the study To ensure compliance participants will undergo direct observation of dosing each day of the week prior to PK visits using the aforementioned strategies
Following Baseline evaluation eligible participants will receive 300 milligrams mg TDF200 mg FTC Truvada once daily for seven days using direct observation approaches to achieve steady state drug PrEP concentrations After one week of therapy participants will undergo intensive PK analysis as well as collection of colorectal biopsies for PD testing PK1 During the PK-intensive day iohexol will be administered intravenously for the empirical determination of renal function and measured glomerular filtration rate mGFR While concurrently on PrEP participants will then be intramuscularly administered depot leuprolide acetate 1125 mg Lupron Two weeks post-injection when testosterone concentrations are far below the lower limit of normal of total testosterone in men typically 200 ngdL or 2 ngmL sampling for PK PD and renal function will be performed PK2
Participants will then immediately begin low-dose oral estrogen therapy 1 mg 17β-estradiol in conjunction with PrEP for one week at which time samples will be collected for the analyses described above PK3 While still on PrEP participants will then transition to high-dose estrogen therapy 6 mg 17β-estradiol for the remainder of the study One week post-high dose estrogen therapy in the presence of PrEP pharmacologic and renal samples will be collected for analysis PK4 PrEP will then be discontinued and two weeks later samples will be collected to assess renal function and hormonal concentrations and evaluate the presence of any remaining PrEP in plasma Peripheral Blood Mononuclear Cells PBMC or colorectal tissue though it should be near undetectable levels for most analytes according to the investigators prior dataPK5
Safety assessments including historyphysical chemistryhematology labs at screening and interim history will be performed at each study-intensive visit Additionally periodic assessments of gender dysphoria will be conducted at baseline and a convenient time during PK visits throughout the study To ensure compliance participants will undergo direct observation of dosing each day of the week prior to PK visits using the aforementioned strategies
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01AI145675 | NIH | None | httpsreporternihgovquickSearchR01AI145675 |