Clinical trial NCT04535934: Novel Approaches for Quantitative Assessment of Adherence
Official title: Novel Approaches for Quantitative Assessment of Adherence
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Healthy
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2020-09-02
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy adult participants with no contraindicated medical conditions or medications.

Brief summary: Approximately 12 adults subjects will be enrolled. Participants will be randomized to one of two directly observed dosing regimens with 2mg adenine 5+ (five stable-labeled nitrogens) as follows: 1 dose/week followed by 4 doses/week OR 3 doses/week followed by 7 doses/week. Each dose regimen will have a duration of approximately 12 weeks and will be separated by a 12-week washout period for a total study duration of approximately 36 weeks.

Dried blood spots (DBS) and whole blood will be collect weekly. Urine will be collected less frequently, about every 2 weeks. The ratio of ATP 5+ to naturally occurring ATP 2+ is dried blood spots will be the primary outcome, as adenine is phosphorylated to ATP in red blood cells. Breakdown products will be measured in urine.

Investigators will allow flexibility in terms of which days are used for dosing for the 1, 3, and 4 dose(s)/week regimens. This is scientifically justified as investigators expect a 20-30 day half-life of ATP 5+ in DBS.

Detailed description: Approximately twelve healthy adult volunteers with no contraindicated medical conditions or medications will be recruited from CU/Denver and the surrounding community.

Participants will be randomized to one of 2 sequences consisting of two directly observed dosing regimens with 2mg adenine 5+ per dose, 1 dose/week followed by 4 doses/week or 3 doses/week followed by 7 doses/week. Each dose regimen will have a duration of approximately 12 weeks and will be separated by an approximately 12-week washout period for a total study duration of approximately 36 weeks. The rationale for this study design is several fold. First, the lower doses are given initially to minimize the potential effects of carry-over in the second regimen. Second, 1 to 7 doses/week encompass a wide range of simulated adherence rates to assess the promise of this taggant, adenine 5+, as an adherence biomarker. Third, the 12 week duration is designed to achieve \~90% of steady-state given an estimated half-life of 20-30 days.

Eligibility criteria: Inclusion:

1. Ambulatory 18-40 year old adults.
2. Ability to comply with study procedures, including directly observed dosing visits and availability and use of video streaming technology.

Exclusion:

1. Inability to give informed consent
2. Pregnancy or plan to become pregnant in the next 12 months or unwillingness to use birth control
3. Current breastfeeding
4. Active psychiatric illness, social condition, or alcohol/drug abuse that, in the opinion of the investigators, would interfere with study requirements.
5. GFR estimate \< 60 ml/min (MDRD equation).
6. Total bilirubin and/or hepatic transaminases (ALT and AST) ≥ 2.5x upper limit of normal
7. Absolute neutrophil count ≤ 1,500/mm3, platelets count ≤ 100,000/mm3, or hemoglobin ≤ 10 g/dL.
8. Symptomatic hemoglobinopathies or active hemolysis.
9. Any laboratory value or uncontrolled medical conditions that, in the opinion of the investigators, would interfere with the study conditions such as, heart disease and/or cancer.
10. Any investigational agents within 30 days of enrollment.
11. Plan to donate blood or plasma during study enrollment.

Primary outcomes:
measure: Ratio of ATP 5+ to ATP 2+ in DBS
timeFrame: 9 months
measure: Dose-proportionality ATP 5+ to ATP 2+ in DBS
timeFrame: 9 months
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado- Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Peter Anderson, PharmD
role: PRINCIPAL_INVESTIGATOR
References: