Clinical trial NCT06132386: Analysis of Cellular Kinases and Aging in PBMCs and Colorectal Tissue
Official title: Analysis of Cellular Kinases and Aging in PBMCs and Colorectal Tissue
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Aging
Keywords: tenofovir
pharmacokinetic
cellular kinase
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: National Institute on Aging (NIA)
First posted: 2023-11-15
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Amount and activity of AK2 in colorectal tissue
timeFrame: Once within one month
measure: Amount and activity of CKM in colorectal tissue
timeFrame: Once within one month
measure: Amount and activity of AK2 in peripheral blood mononuclear cells
timeFrame: Once within one month
measure: Amount and activity of CKM in peripheral blood mononuclear cells
timeFrame: Once within one month
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Craig Hendrix, MD
role: PRINCIPAL_INVESTIGATOR
References: