Novel Approaches for Quantitative Assessment of Adherence

Completed

• Conditions: Healthy
• Interventions: Other: Adenine 5+ (five stable-labeled nitrogens)

• Registration Number: NCT04535934
• Lead Sponsor: University of Colorado, Denver

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.

Study Timeline

• Study First Submitted: 2020-02-14
• Study Start: 2020-08-31
• Study First Submitted QC: 2020-09-01
• Study First Posted: 2020-09-02
• Primary Completion: 2022-11-15
• Study Completion: 2022-11-15
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-20
• Last Update Posted: 2024-05-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
3 doses/week followed by 7 doses/week.	Adenine 5+ (five stable-labeled nitrogens)	Directly observed dosing regimen with 2 mg adenine 5+ (five stable-labeled nitrogens) as follows: 3 doses/week followed by 7 doses/week. The duration of each dosing regimen will be approximately 12 weeks. A washout period of approximately 12 weeks will separates the dosing regimens.
1 dose/week followed by 4 doses/week	Adenine 5+ (five stable-labeled nitrogens)	Directly observed dosing regimen with 2 mg adenine 5+ (five stable-labeled nitrogens) as follows: 1 dose/week followed by 4 doses/week. The duration of each dosing regimen will be approximately 12 weeks. A washout period of approximately 12 weeks will separates the dosing regimens.

Primary Outcome Measures

Name	Time	Method
Ratio of ATP 5+ to ATP 2+ in DBS	9 months	Ratio of ATP 5+ to ATP 2+ in DBS following directly observed therapy with 2mg of adenine 5+ at 1, 3, 4, and 7 doses/week
Dose-proportionality ATP 5+ to ATP 2+ in DBS	9 months	Dose-proportionality to relate ATP 5+ to ATP 2+ in DBS with adherence rate.

Trial Locations

Locations (1)

University of Colorado- Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States