IMPAACT P1080: Psychiatric and Antiretroviral Medication Concentrations in HIV-infected and Uninfected Children and Adolescents

NCT01232361 | Completed

• 1 other identifier: IMPAACT P1080
• Study Type: observational
• Target: 127
• Locations: 2 countries
• Sites: 22

Brief Summary

The main purpose of this study is to find out how stimulant medications (methylphenidate or amphetamine/ dextroamphetamine) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD)are processed in HIV-1 infected and HIV-uninfected children and adolescents.

Conditions

ADHD; HIV

Keywords

ADHD; HIV; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Estimation of steady-state oral clearance (Cl/F) for each psychiatric study medication is the primary outcome.

  Additional pharmacokinetic parameters \[area under the concentration-time curve (AUC), apparent volume of distribution (Vd/F), half-life (t½), pre-dose concentration (Cpre), maximum concentration (Cmax), corresponding time of maximum concentration (Tmax), elimination rate constant (ke), and between and within-subject variability\] for the selected psychiatric medications in HIV-1 infected and uninfected children and adolescents will also be determined.

  duration of study

Study Arms (2)

Methylphenidate

Subjects will be stratified by medication, HIV status and HIV antiretroviral therapy as follows: Stratum A - 15 HIV uninfected subjects; Stratum B - 15 HIV-1 infected subjects who are taking concomitant (prescribed) efavirenz; Stratum C - 15 HIV-1 infected subjects who are taking a (prescribed) protease inhibitor (PI)\* with concomitant ritonavir (at boosting doses) or lopinavir/ritonavir. \*PI may be any of the following: atazanavir, darunavir, fosamprenavir, indinavir, saquinavir or tipranavir

Amphetamine / dextroamphetamine

Subjects will be stratified by medication, HIV status and HIV antiretroviral therapy as follows: Stratum A - 15 HIV uninfected subjects; Stratum B - 15 HIV-1 infected subjects who are taking concomitant (prescribed) efavirenz; Stratum C - 15 HIV-1 infected subjects who are taking a (prescribed) protease inhibitor (PI)\* with concomitant ritonavir (at boosting doses) or lopinavir/ritonavir. \*PI may be any of the following: atazanavir, darunavir, fosamprenavir, indinavir, saquinavir or tipranavir

Eligibility Criteria

• Age: 6 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

HIV-1 infected and uninfected children and adolescents ages ≥6 to \<25 years who are currently receiving methylphenidate or amphetamine/dextroamphetamine for treatment of attention deficit hyperactivity disorder (ADHD)

You may qualify if:

• Children and adolescents age ≥6 to \<25 years at entry.
• Documented HIV-1 infection defined as positive test results obtained from 2 different samples. Tests may include two of the same type OR two different types of tests listed below, as long as they are positive test results obtained from the 2 different samples:
• HIV-1 DNA PCR
• HIV-1 culture
• HIV-1 RNA PCR \> 5,000 copies/mL
• HIV-1 p24 antigen detection
• HIV-1 antibody test (any licensed ELISA test kit, and confirmation by either serum HIV-1 antigen test, HIV-1 antibody test done by a method that is not an ELISA, Western blot, or plasma HIV-1 RNA)
• Subject must be taking antiretroviral medications for clinical care for at least 4 weeks prior to pharmacokinetic sampling, with no changes in drugs, doses or formulations.
• Subject must be taking either efavirenz (EFV) OR a PI with ritonavir (RTV) OR lopinavir/ritonavir as part of combination antiretroviral therapy. Note that RTV dosing must be as a "booster" for the protease inhibitor. Protease inhibitors may be any of the following: atazanavir, darunavir, fosamprenavir, indinavir, saquinavir or tipranavir. Subjects may not be taking more than one full-dose PI. Subjects may not be taking EFV in addition to lopinavir/ritonavir or other PI.
• Subject must be taking methylphenidate or amphetamine/ dextroamphetamine for treatment of ADHD for at least 1 week prior to enrollment.
• Allowable methylphenidate formulations include: immediate-release (Methylin, Ritalin or other generic, Focalin), sustained-release (Ritalin SR, Metadate ER or generic), or biphasic (Ritalin LA, Metadate CD, Concerta, Focalin XR).
• Allowable formulations for amphetamine/ dextroamphetamine include: Adderall, Adderall XR, Dexedrine, Liquadd, and Dexedrine Spansules(and any generic equivalents).
• For both study arms, any dose up to the maximum FDA-approved dose by age will be allowed.
• Subjects must be able to come in for PK sampling after at least 2 days of consecutive, uninterrupted psychiatric and antiretroviral medication delivery.
• Parent/primary caregiver, subjects \>18 years or emancipated minors must be able and willing to provide signed informed consent. Assent of the minor subject should be obtained where required per site procedures and IRB recommendations.

You may not qualify if:

• A positive urine test at screening for use of the following disallowed drugs: methamphetamine; methadone, barbiturates; benzodiazepines; opiates; phencyclidine; or propoxyphene.
• Note: If propoxyphene is not part of the routine screening panel at the site, it is not required. If propoxyphene is part of the routine screening panel at the site, the results should be recorded on the appropriate CRF.
• Chemotherapy for malignancy within three months prior to study screening.
• Pregnancy or breastfeeding an infant.
• Any clinically significant diseases (other than HIV-1 infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study.
• Study drugs prescribed above the FDA-recommended maximum dose by age.
• Known or demonstrated hypersensitivity or intolerance to Dextromethorphan.
• Subjects taking a disallowed medication.
• For HIV-1 Infected Subjects Only: Presence of an active CDC Stage C (per 1994 Revised Classification System for Human Immunodeficiency Virus Infection in Children Less Than 13 Years of Age, or 1993 Revised Classification System for HIV Infection Among Adolescents and Adults) opportunistic infection or serious bacterial infection requiring therapy within two weeks prior to screening.

Sponsors & Collaborators

• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: lead

Study Sites (22)

Univ. of Alabama Birmingham NICHD CRS (5096)

Birmingham, Alabama, 35294, United States

Location

Miller Children's Hospital Long Beach (5093)

Long Beach, California, 90806, United States

Location

Usc La Nichd Crs (5048)

Los Angeles, California, 90033, United States

Location

UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CR (3601)

Los Angeles, California, 90095, United States

Location

Univ of California, San Diego (UCSD) (4601)

San Diego, California, 92103, United States

Location

Childrens Hospital (U. Colorado, Denver) NICHD CRS (5052)

Denver, Colorado, 80218-1088, United States

Location

Children's National Med. Ctr. Washington DC NICHD CRS (5015)

Washington D.C., District of Columbia, 20010, United States

Location

South Florida CDC Ft Lauderdale NICHD CRS (5055)

Fort Lauderdale, Florida, 33316, United States

Location

Univ of Miami Pediatric/Perinatal HIV/AIDS (4201)

Miami, Florida, 33136, United States

Location

Chicago Children's CRS (4001)

Chicago, Illinois, 60611, United States

Location

Rush University Cook County Hospital NICHD CRS (5083)

Chicago, Illinois, 60612, United States

Location

Johns Hopkins University NICHD CRS (5092)

Baltimore, Maryland, 21287, United States

Location

Boston Medical Center Ped. HIV Program NICHD CRS (5011)

Boston, Massachusetts, 02118, United States

Location

WNE Maternal Pediatric Adolescent AIDS CRS (7301)

Worcester, Massachusetts, 01605, United States

Location

Wayne State University/Children's Hospital of Michigan NICHD CRS (5041)

Detroit, Michigan, 48201, United States

Location

New York University NY (5012)

New York, New York, 10016, United States

Location

Columbia IMPAACT Center (4101)

New York, New York, 10032, United States

Location

SUNY Stony Brook (5040)

Stony Brook, New York, 11794-8111, United States

Location

Jacobi Med. Ctr. Bronx NICHD CRS (5013)

The Bronx, New York, 10461, United States

Location

St. Jude Childrens Research Hospital, Memphis (6501)

Memphis, Tennessee, 38105-2794, United States

Location

Texas Children's Hosp. CRS (3801)

Houston, Texas, 77030, United States

Location

San Juan City Hosp. PR NICHD CRS (5031)

San Juan, 00927, Puerto Rico

Location

Biospecimen

Retention: SAMPLES WITH DNA

Non-viable PBMC pellets for DNA genotypic analysis

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Brookie Best, MD

  University of California, San Diego/IMPAACT

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2010
• First Posted: November 2, 2010
• Study Start: October 8, 2010
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: August 3, 2021

Record last verified: 2021-07

Locations

US (21); PR (1)