Analysis of Cellular Kinases and Aging in PBMCs and Colorectal Tissue

The goal of this clinical study is to learn about the effect of aging on certain enzymes, or proteins, in the blood and colon. The study involves collection of blood and colon tissue biopsies using a flexible sigmoidoscope or colonoscope. This study is also investigating how medications tenofovir and emtricitabine interact with certain enzymes. The investigators will compare the difference in enzyme activity between people taking tenofovir and emtricitabine, to those who are not taking tenofovir and emtricitabine.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Aging
• Intervention / Treatment: Other: biopsy

Detailed Description

This project involves obtaining peripheral blood mononuclear cells (PBMCs) and colorectal tissue samples from study participants in order to measure adenylate kinase 2 (AK2) and muscle-type creatine kinase (CKM) enzyme levels in various age populations. Both AK2 and CKM has been demonstrated to be vital enzymes in converting the prodrug tenofovir (TFV) into its active form, tenofovir diphosphate (TFV-DP). However, no study has yet investigated the effect of aging on AK2 or CKM in tissues relevant to HIV infection and prevention. This study will investigate the AK2 and CKM variability in individuals from various age groups and how the pharmacokinetics (PK) of tenofovir (TFV) vary with altering levels of cellular enzymes in different age populations

• Study Type: Observational
• Enrollment (Actual): 21

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Study population include adults between the ages of 18-50 and 65-80. The population recruited will include healthy volunteers and persons on HIV treatment or prevention that contains tenofovir.

Description

Inclusion Criteria:

1. English speaking male or female volunteers between the ages of 18-50 for younger adults or 65-80 for older adults
2. Willing to provide written informed consent
3. Willing to abstain from insertion of anything in rectum for 72 hours before and 72 hours after the endoscopic procedure for colorectal tissue collection.
4. Not currently participating in other research studies involving drugs and/or medical devices.

For participants not infected with HIV (Control Cohort A)

1. No known risk for HIV exposure or a documented negative HIV-1/HIV-2 Ag/Ab test in the past 3 months (HIV risk, but not on PrEP)
2. Documented negative HBsAg in those taking study TFV (i.e. cohort B)

For participants not infected with HIV, but taking or willing to take TFV (PrEP Cohort B)

1. Currently taking TFV-based oral PrEP daily or willing to take oral TFV-containing PrEP for one week
2. Documented negative HIV-1/HIV-2 Ag/Ab test in the past 3 months
3. Documented negative HBsAg

For participants infected with HIV (ARV Cohort C)

1. Virologically suppressed HIV for at least 6 months prior to screening.
2. Taking tenofovir disoproxil fumarate or tenofovir alafenamide containing regimen to treat HIV

Exclusion Criteria:

1. History of inflammatory bowel disease or active inflammatory condition of the GI tract
2. History of significant gastrointestinal bleeding
3. Current medically-indicated use of warfarin or heparin or other anticoagulant medications associated with increased risk for bleeding following mucosal biopsy (e.g., daily high dose aspirin [>81 mg], non-steroidal anti-inflammatory drugs [NSAIDs], or Pradaxa®)
4. Use of systemic immunomodulatory medications within 4 weeks of enrollment
5. Use of rectally administered medications within 4 weeks of enrollment
6. Use of product containing nonoxynol-9 within 4 weeks of enrollment
7. Use of any investigational products within 4 weeks of enrollment
8. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease.

9. Active rectal infection (GC, Chlamydia, HSV). Participants screening positive for GC/CT at the time of endoscopy will be excluded from analysis (and replaced).

   For participants not undergoing a concurrent endoscopic procedure for indication unrelated to this study:

10. Hct <36%
11. Platelet count <150/mm3
12. International normalised ratio blood test > 1.2

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Volunteers, not taking Tenofovir (TFV) based PrEP	Other: biopsy; colorectal biopsy for tissue acquisition
Healthy volunteers, steady state Tenofovir (TFV) based regimen	Other: biopsy; colorectal biopsy for tissue acquisition
Persons infected with HIV taking Tenofovir (TFV) and emtricitabine (FTC) based HIV treatment	Other: biopsy; colorectal biopsy for tissue acquisition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of AK2 in Colorectal Tissue	Concentration in nanometers (nm) of AK2 in colorectal tissue.	Once within one month
Concentration of CKM in Colorectal Tissue	Concentration in nanometers (nm) of CKM in colorectal tissue	Once within one month
Concentration of AK2 in Peripheral Blood Mononuclear Cells	Concentration in nanometers (nm) of AK2 in peripheral blood mononuclear cells	Once within one month

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Aging (NIA)
• Investigators: Principal Investigator: Craig Hendrix, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2023
• Primary Completion (Actual): May 20, 2024
• Study Completion (Actual): May 20, 2024

Study Registration Dates

• First Submitted: October 20, 2023
• First Submitted That Met QC Criteria: November 6, 2023
• First Posted (Actual): November 15, 2023

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: tenofovir; pharmacokinetic; cellular kinase
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Biopsy
• Other Study ID Numbers: IRB00307426; R56AI161030-01A1 (U.S. NIH Grant/Contract); R01AG064908-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No