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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Sponsor:
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01232361
First received: October 29, 2010
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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.


Condition
ADHD
HIV

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: IMPAACT P1080: Psychiatric and Antiretroviral Medication Concentrations in HIV-infected and Uninfected Children and Adolescents

Resource links provided by NLM:


Further study details as provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Estimation of steady-state oral clearance (Cl/F) for each psychiatric study medication is the primary outcome. [ Time Frame: duration of study ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples With DNA

Non-viable PBMC pellets for DNA genotypic analysis


Estimated Enrollment: 90
Study Start Date: September 2010
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
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


Detailed Description:

P1080 is a pilot population pharmacokinetic study of HIV-1 infected and uninfected children and adolescents who are taking methylphenidate or amphetamine/ dextroamphetamine for the treatment of ADHD. Prescribing various psychiatric medications in combination with antiretroviral regimens is a standard clinical practice occurring without adequate evidence regarding benefits and risks. The goals of this study are to determine plasma concentrations of psychiatric and antiretroviral medications in children and adolescents. Psychiatric medication dose requirement and exposure in HIV-1 infected subjects will be compared to that seen in uninfected children and adolescents, and antiretroviral exposure will be compared to published studies in children and adolescents.

  Eligibility

Ages Eligible for Study:   6 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)

Criteria

Inclusion Criteria for HIV-1 Infected Subjects

  • 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.
  • Female subjects of reproductive potential (having reached menses, or not having reached menopause or not having undergone hysterectomy, bilateral oophorectomy, or tubal ligation) who engage in sexual activity that could lead to pregnancy must agree to avoid pregnancy during the entire trial and to consistently and appropriately use at least two of the following contraception methods: condoms, diaphragm or cervical cap with spermicide, IUD, hormonal-based contraception. A list of acceptable methods can be found at the FDA Birth Control Guide (http://www.fda.gov/fdac/features/1997/babyguide.pdf).

    • Note: "Female subjects of reproductive potential" is defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months (e.g. who have had menses within the preceding 24 months), or have not undergone a sterilization procedure (hysterectomy, bilateral oophorectomy or salpingotomy). If the female subject is not of reproductive potential, she is eligible without requiring contraception.

Inclusion Criteria for HIV Uninfected Subjects

  • Children and adolescents age ≥6 to <25 years at entry.
  • Subject is not known to be HIV-1 infected.

    • Note: For perinatally-exposed subjects, definitive exclusion of HIV-1 infection in a non-breastfed infant is based on two or more negative virologic tests, with one obtained at age ≥1 month and one at ≥4 months, or two negative HIV-1 antibody tests from separate specimens obtained at age ≥6 months. Per current CDC guidelines, uninfected subjects ≥13 years will be screened for HIV-1. A documented negative HIV-1 antibody screening test or negative HIV-1 RNA or DNA PCR within the past year will be accepted to fulfill this criterion.
  • Subject must be taking methylphenidate or amphetamine/ dextroamphetamine for treatment of ADHD for at least one week prior to enrollment.

    • Allowable methylphenidate formulations include: immediate-release (Methylin, Ritalin or other generic, Focalin), sustained-release (Methylin ER, Ritalin SR, Metadate ER or generic), or biphasic (Ritalin LA, Metadate CD, Concerta and Focalin XR.
    • Allowable formulations for amphetamine/ dextroamphetamine include: Adderall, Adderall XR, Dexedrine, Liquadd, and Dexedrine Spansules (and any generic equivalents).
    • For both 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 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.
  • Female subjects of child bearing potential (having reached menses, or not having reached menopause or not having undergone hysterectomy, bilateral oophorectomy, or tubal ligation) who engage in sexual activity that could lead to pregnancy must agree to avoid pregnancy during the entire trial and to consistently and appropriately use at least two of the following contraception methods: condoms, diaphragm or cervical cap with spermicide, IUD, hormonal-based contraception. A list of acceptable methods can be found at the FDA Birth Control Guide (http://www.fda.gov/fdac/features/1997/babyguide.pdf).

    • Note: "Female subjects of child bearing potential" is defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months (e.g. who have had menses within the preceding 24 months), or have not undergone a sterilization procedure (hysterectomy, bilateral oophorectomy or salpingotomy). If the female subject is not of child bearing potential, she is eligible without requiring contraception.

Exclusion Criteria for All Study Subjects

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01232361

  Hide Study Locations
Locations
United States, Alabama
Univ. of Alabama Birmingham NICHD CRS (5096) Recruiting
Birmingham, Alabama, United States, 35294
Contact: Sharan Robbins, B.A.    205-996-6418    srobbins@peds.uab.edu   
Principal Investigator: Marilyn J Crain, M.P.H., M.D.         
United States, California
Miller Children's Hospital Long Beach (5093) Recruiting
Long Beach, California, United States, 90806
Contact: Janielle Jackson-Alvarez, RN    562-933-8666    jjackson-alvarez@memorialcare.org   
Principal Investigator: Audra Deveikis, MD         
Usc La Nichd Crs (5048) Recruiting
Los Angeles, California, United States, 90033
Contact: Eva A. Operskalski, PhD    323-226-2226    eva@usc.edu   
Principal Investigator: Andrea Kovacs, MD         
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CR (3601) Recruiting
Los Angeles, California, United States, 90095
Contact: Michele Carter    310-794-6780    mfcarter@mednet.ucla.edu   
Principal Investigator: Jaime Deville, MD         
Univ of California, San Diego (UCSD) (4601) Recruiting
San Diego, California, United States, 92103
Contact: Jean Manning, R.N., B.S.N.    858-534-9216    jmmanning@ucsd.edu   
Principal Investigator: Stephen A Spector, M.D.         
Univ. of California San Francisco NICHD CRS (5091) Recruiting
San Francisco,, California, United States, 94117
Contact: Megan Miller    415-476-9373    millermj@peds.ucsf.edu   
Principal Investigator: Diane Wara, MD         
Harbor (UCLA) Medical Center NICHD CRS (5045) Recruiting
Torrance, California, United States, 90502
Contact: Judy Hayes, BSN, RN    310-781-3627    jhayes@labiomed.org   
Principal Investigator: Margaret Keller, MD         
United States, Colorado
Childrens Hospital (U. Colorado, Denver) NICHD CRS (5052) Recruiting
Denver, Colorado, United States, 80218-1088
Contact: Emily A. Barr, C.P.N.P    720-777-6752    barr.emily@tchden.org   
Principal Investigator: Myron Levin, M.D.         
United States, District of Columbia
Children's National Med. Ctr. Washington DC NICHD CRS (5015) Recruiting
Washington, District of Columbia, United States, 20010
Contact: Romuladus E. Azuine, MPH    202-476-3074    razuine@cnmc.org   
Principal Investigator: Steven L. Zeichner, MD, PhD         
Howard University Washington DC NICHD CRS (5044) Recruiting
Washington, District of Columbia, United States, 20060
Contact: Patricia Houston    202-865-4578    phouston@howard.edu   
Principal Investigator: Sohail R. Rana, MD         
United States, Florida
South Florida CDC Ft Lauderdale NICHD CRS (5055) Recruiting
Ft Lauderdal, Florida, United States, 33316
Contact: Lisa Bridges, RN    954-728-1125    LBridges@browardhealth.org   
Principal Investigator: Ana Puga, MD         
Univ of Miami Pediatric/Perinatal HIV/AIDS (4201) Recruiting
Miami, Florida, United States, 33136
Contact: Patricia Bryan    305-243-4447    pbryan@med.miami.edu   
Principal Investigator: Charles D Mitchell, M.D.         
United States, Illinois
Chicago Children's CRS (4001) Recruiting
Chicago, Illinois, United States, 60611
Contact: Margaret A Sanders, MPH    312-227-8275    msanders@luriechildrens.org   
Principal Investigator: Ram Yogev, MD         
Rush University Cook County Hospital NICHD CRS (5083) Recruiting
Chicago, Illinois, United States, 60612
Contact: Maureen McNichols, RN, MSN    312-572-4541    maureen_mcnichols@rush.edu   
Principal Investigator: James B. McAuley, MD, MPH         
United States, Maryland
Johns Hopkins University NICHD CRS (5092) Recruiting
Baltimore, Maryland, United States, 21287
Contact: Todd Noletto, MPH    443-287-9040    tnolett1@jhmi.edu   
Principal Investigator: Jonathan M. Ellen, M.D.         
United States, Massachusetts
Boston Medical Center Ped. HIV Program NICHD CRS (5011) Recruiting
Boston, Massachusetts, United States, 02118
Contact: Laureen Kay, RN    617-414-3632    laureen.kay@bmc.org   
Principal Investigator: Stephen I. Pelton, MD         
Children's Hospital of Boston (5009) Recruiting
Boston, Massachusetts, United States, 02115
Contact: Catherine Kneut, RN, MS, CRNP    617-355-7879    catherine.kneut@childrens.harvard.edu   
Principal Investigator: Sandra K. Burchett, MD, MS         
WNE Maternal Pediatric Adolescent AIDS CRS (7301) Recruiting
Worcester, Massachusetts, United States, 01605
Contact: Margaret McManus    508-856-5589    Margaret.McManus@umassmed.edu   
Principal Investigator: Katherine Luzuriaga, MD         
United States, Michigan
Wayne State University/Children's Hospital of Michigan NICHD CRS (5041) Recruiting
Detroit, Michigan, United States, 48201
Contact: Ulyssa Hancock, R.N., B.S.N.    313-745-9204    uhancock@dmc.org   
Principal Investigator: Chokechai Rongkavilit, MD         
United States, New Jersey
New Jersey Medical School (2802) Recruiting
Newark, New Jersey, United States, 07103
Contact: Linda Bettica, RN    973-972-3119    betticlm@umdnj.edu   
Principal Investigator: Arry Dieudonne, MD         
United States, New York
Bronx-Lebanon Hospital (6901) Recruiting
Bronx, New York, United States, 10457
Contact: Mary-Elizabeth Vachon, MPH    718-960-1016    mvachon@bronxleb.org   
Principal Investigator: Murli U. Purswani, MD         
Jacobi Med. Ctr. Bronx NICHD CRS (5013) Recruiting
Bronx, New York, United States, 10461
Contact: Marlene Burey    718-918-4783    marlene.burey@nbhn.net   
Principal Investigator: Andrew Wiznia, MD         
Columbia IMPAACT Center (4101) Recruiting
New York, New York, United States, 10032
Contact: Alice Higgins, RN, MPA    212-305-8181    ah310@columbia.edu   
Principal Investigator: Phillip LaRussa         
Metropolitan Hospital (5003) Recruiting
New York, New York, United States, 10029
Contact: Santa Paul    212-423-8630    santa.paul@nychhc.org   
Principal Investigator: Marukh Bamji, MD         
New York University NY (5012) Recruiting
New York, New York, United States, 10016
Contact: Joseph Bertran    212-263-8198    Joseph.bertran@nyumc.org   
Principal Investigator: William Borkowsky, M.D.         
SUNY Stony Brook (5040) Recruiting
Stony Brook, New York, United States, 11794-8111
Contact: Denise M Ferraro, M.S., FNP-BC    631-444-8225    denise.ferraro@stonybrook.edu   
Principal Investigator: Sharon A Nachman, M.D.         
United States, North Carolina
Duke Pediatric Infectious Diseases (DUMC) (4701) Recruiting
Durham, North Carolina, United States, 27710-3499
Contact: John Swetnam, MEd    919-668-4847    swetnam@duke.edu   
Principal Investigator: Coleen Cunningham, MD         
United States, Pennsylvania
Childrens Hospital of Philadelphia (6701) Recruiting
Philadelphia, Pennsylvania, United States, 19104-4318
Contact: Carol A. Vincent, CRNP, MSN    215-590-2262    vincentc@email.chop.edu   
Principal Investigator: Steven Douglas, MD         
United States, Tennessee
St. Jude Childrens Research Hospital, Memphis (6501) Recruiting
Memphis, Tennessee, United States, 38105-2794
Contact: Laura Jill Utech, RN, MSN, CCRC    (901) 595-3490    jill.utech@stjude.org   
Principal Investigator: Patricia Flynn, MD, MS         
United States, Texas
Texas Children's Hosp. CRS (3801) Recruiting
Houston, Texas, United States, 77030
Contact: Chivon D. Jackson, B.S.N., A.D.N.    1-832-824-1319    CDJACKSO@texaschildrenshospital.org   
Puerto Rico
San Juan City Hosp. PR NICHD CRS (5031) Recruiting
San Juan, Puerto Rico, 00927
Contact: Lizbeth Fábregas -Troche, M.S.    787-764-3083    lfabregas@SanJuanCapital.com   
Principal Investigator: Midnela Acevedo-Flores, M.T., M.D.         
Sponsors and Collaborators
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Investigators
Study Chair: Brookie Best, MD University of California, San Diego/IMPAACT
  More Information

No publications provided

Responsible Party: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01232361     History of Changes
Other Study ID Numbers: IMPAACT P1080
Study First Received: October 29, 2010
Last Updated: May 16, 2014
Health Authority: United States: Federal Government

Keywords provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group:
ADHD
HIV
Pharmacokinetics

Additional relevant MeSH terms:
Adderall
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 11, 2014