Examining Hair to Determine Tenofovir Exposure - Full Text View

Sponsored by:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00903084

Purpose

This study will determine whether a hair test can reveal how much of the anti-HIV medication tenofovir a person without HIV has been exposed to.

Condition	Intervention	Phase
HIV	Drug: Tenofovir Disoproxil Fumarate	Phase I

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Crossover Assignment, Pharmacokinetics Study
Official Title:	A Phase 1 Pharmacokinetic Study of Varying Dosing Patterns on Tenofovir Concentrations in Hair

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

Tenofovir hair concentration under each dosing condition [ Time Frame: Measured 6 weeks after starting each dosing condition ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	June 2009
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Participants will receive 7 doses per week, then 4 doses per week, then 2 doses per week (each for 6 weeks) of tenofovir, with a break in between dosing periods.	Drug: Tenofovir Disoproxil Fumarate 300-mg tablet
2: Active Comparator Participants will receive 7 doses per week, then 2 doses per week, then 4 doses per week (each for 6 weeks) of tenofovir, with a break in between dosing periods.	Drug: Tenofovir Disoproxil Fumarate 300-mg tablet
3: Active Comparator Participants will receive 4 doses per week, then 7 doses per week, then 2 doses per week (each for 6 weeks) of tenofovir, with a break in between dosing periods.	Drug: Tenofovir Disoproxil Fumarate 300-mg tablet
4: Active Comparator Participants will receive 4 doses per week, then 2 doses per week, then 7 doses per week (each for 6 weeks) of tenofovir, with a break in between dosing periods.	Drug: Tenofovir Disoproxil Fumarate 300-mg tablet
5: Active Comparator Participants will receive 2 doses per week, then 7 doses per week, then 4 doses per week (each for 6 weeks) of tenofovir, with a break in between dosing periods.	Drug: Tenofovir Disoproxil Fumarate 300-mg tablet
6: Active Comparator Participants will receive 2 doses per week, then 4 doses per week, then 7 doses per week (each for 6 weeks) of tenofovir, with a break in between dosing periods.	Drug: Tenofovir Disoproxil Fumarate 300-mg tablet

Detailed Description:

Pre-exposure prophylaxis (PrEP) is a new strategy for the prevention of HIV infection. It involves providing antiretroviral medications—those that treat HIV infections—to people before they are exposed to HIV. In clinical trials of PrEP, several of which are currently under way, accurate measurements are needed of how much exposure participants have to the PrEP medications. Current methods, such as self-reports of medication adherence or pill counting, can lead to inaccurate readings of PrEP exposure because participants may forget to take pills and individual differences may affect levels of exposure. Measuring PrEP exposure levels in hair yields an objective marker of exposure that is not subject to self-report errors and that takes into account individual differences.

This study will test the use of a hair sample for assessing the level of exposure to tenofovir disoproxil fumarate (TDF), an antiretroviral medication, in people not infected with HIV.

Participation in this study will last 9 months. Participants will undergo baseline testing and then will be randomly assigned to begin one of three conditions, based on dosing schedule: receiving TDF 2, 4, or 7 days per week. All participants will complete each of these dosing schedules, but the order in which they are completed will be randomly assigned. Each dosing schedule will last 6 weeks, with a break of several weeks between them.

During each dosing schedule, study staff will confirm that participants are taking each scheduled dose by watching them take the pills on weekdays and calling them on weekends. Follow-up visits will occur at Days 1, 21, and 42 of each dosing schedule. During the baseline and follow-up visits, the following will be completed: an HIV rapid test; counseling about HIV prevention; a brief physical exam; a talk with a staff member about health, symptoms, and other medications; a blood draw, which will be used for several tests; collection of a urine sample and pregnancy test; and optional donation of a sample of pubic hair. On the last day of each dosing schedule, a small sample of hair will be cut from each participant's scalp. An additional follow-up visit will occur after participants complete 4 weeks of the 7-day dosing schedule. This visit will last 24 hours and will involve collection of additional blood samples.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Ability to speak English
HIV-1 uninfected, based on HIV rapid testing performed during screening and enrollment
Calculated creatinine clearance greater than or equal to 60 mL/min by the Cockcroft-Gault creatinine clearance formula
Serum creatinine less than or equal to the site laboratory upper limit of normal
Urine dipstick with negative or trace result for both glucose and protein
Negative urine beta human chorionic gonadotropin (beta-HCG) test for women
Adequate hepatic function, defined as total bilirubin and hepatic transaminases (ALT and AST) less than or equal to twice the upper limit of normal
Adequate hematologic function, defined as an absolute neutrophil count greater than or equal to 1,500/mm3, platelet count greater than or equal to 100,000/mm3, and hemoglobin greater than or equal to 10 g/dL
Ability to participate in modified directly observed dosing of study drug
Ability to provide a personal cell phone number to be contacted on for unobserved modified directly observed therapy (mDOT) visits
Minimum length of 3 cm scalp hair in occipital region
Willing to provide hair and plasma samples as specified by the protocol
Dark hair (brown or black), as assessed by the study clinician
Volunteers born female must agree to consistently use effective contraception from at least 21 days prior to enrollment through the last protocol visit for sexual activity that could lead to pregnancy and agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last scheduled protocol visit.

Exclusion Criteria:

Active and serious medical problems, including heart or lung disease, diabetes requiring hypoglycemia medications, previously diagnosed malignancies expected to require further treatment, and serious infections
Hepatitis B surface antigen positivity
History of chronic kidney disease
Known osteoporosis, osteomalacia, or osteopenia
History of pathological bone fractures not related to trauma
Receiving ongoing therapy with any of the following: antiretroviral therapy, interferon or interleukin therapy, aminoglycoside antibiotics, amphotericin B, cidofovir, systemic chemotherapeutic agents, other agents with significant nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), or other investigational agents
Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting that may confer an inability to receive an orally administered medication
Use of hair dyes or hair permanent products in the last 3 months (streaking is acceptable)
Current participation in any other research study involving drugs, investigational agents, or medical devices
Breastfeeding at screening or enrollment, per participant report
Active alcohol or drug use considered sufficient by clinician to hinder compliance with study procedures
Elevated risk of HIV infection, as defined in the study protocol
At enrollment, has any social or medical condition that, in the investigator's opinion, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00903084

Contacts

Contact: Albert Liu, MD, MPH

415-554-9104

albert.liu@sfdph.org

Locations

United States, California
University of California, San Francisco
San Francisco, California, United States, 94122
San Francisco Department of Public Health
San Francisco, California, United States, 94102

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Study Chair:

Albert Liu, MD, MPH

San Francisco Department of Public Health

More Information

Additional Information:

Click here for the San Francisco Department of Public Health HIV Research Section This link exits the ClinicalTrials.gov site

Publications:

Gandhi M, Ameli N, Bacchetti P, Gange SJ, Anastos K, Levine A, Hyman CL, Cohen M, Young M, Huang Y, Greenblatt RM; Women's Interagency HIV Study (WIHS). Protease inhibitor levels in hair strongly predict virologic response to treatment. AIDS. 2009 Feb 20;23(4):471-8.

Huang Y, Gandhi M, Greenblatt RM, Gee W, Lin ET, Messenkoff N. Sensitive analysis of anti-HIV drugs, efavirenz, lopinavir and ritonavir, in human hair by liquid chromatography coupled with tandem mass spectrometry. Rapid Commun Mass Spectrom. 2008 Nov;22(21):3401-9.

Gandhi M, Greenblatt RM. Hair it is: the long and short of monitoring antiretroviral treatment. Ann Intern Med. 2002 Oct 15;137(8):696-7. No abstract available.

Responsible Party:	San Francisco Department of Public Health ( Albert Liu, MD, MPH )
Study ID Numbers:	R21 MH085598, DAHBR 9A-ASPQ
Study First Received:	May 13, 2009
Last Updated:	June 25, 2009
ClinicalTrials.gov Identifier:	NCT00903084 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):

Pharmacokinetics in Hair
Tenofovir
Pharmacokinetics
Concentrations
Hair

Study placed in the following topic categories:

Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents
HIV Infections
Acquired Immunodeficiency Syndrome

Tenofovir
Antiviral Agents
Reverse Transcriptase Inhibitors
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Tenofovir

Enzyme Inhibitors
Antiviral Agents
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Reverse Transcriptase Inhibitors
Tenofovir disoproxil

ClinicalTrials.gov processed this record on September 10, 2009