Adolescent Master Protocol (AMP)

ClinicalTrials.gov Identifier:
NCT01418014
First received: July 22, 2011
Last updated: October 17, 2014
Last verified: October 2014
  Purpose

The advances in treatment to prevent maternal HIV transmission to neonates have been groundbreaking. As a result, the number of new perinatally-infected children in the U.S. is now small. Subsequent improvements in the treatment of HIV-infected infants and children have been equally remarkable, ensuring that most previously infected American children have survived and are approaching adolescence. In addition, the number of HIV-infected adolescents worldwide is growing substantially in both resource-poor countries and in countries with increasing levels of health care. Therefore, there is a global cohort of children who have been living with HIV infection since birth who are aging into adolescence. Little is definitively known about the impact of HIV infection and its treatment on the maturation process in these children.

AMP is a prospective cohort study designed to define the impact of HIV infection and antiretroviral therapy on pre-adolescents and adolescents with perinatal HIV infection. Domains to be investigated include growth and sexual maturation, metabolic risk factors for cardiovascular disease, cardiac function, bone health, neurologic, neurodevelopment, language, hearing and behavioral function, and sexually transmitted infections (STI).


Condition
HIV/AIDS

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Adolescent Master Protocol

Resource links provided by NLM:


Further study details as provided by Harvard School of Public Health:

Primary Outcome Measures:
  • Abnormal growth [ Time Frame: Annually for 10 years ] [ Designated as safety issue: No ]
    Assessed via measurement of height, weight, skinfold thickness, mid-upper arm and waist and hip circumference, nutrition and physical activity questionnaires ; subjects meeting growth trigger based on height measurements also have the following laboratory assessments: IGF-I, IGFBP-3, and GHBP. A growth hormone stimulation test may also be required at the recommendation of the endocrinologist.

  • Delayed sexual maturation [ Time Frame: Annually for 10 years except if subject reaches Tanner Stage 5 ] [ Designated as safety issue: No ]
    Assessed via tanner staging; subjects meeting the growth trigger based on the results of the tanner staging will also have the following laboratory assessments: morning LH, FSH, estradiol, and testosterone

  • Abnormal bone mineral density [ Time Frame: Two DXAs, two years apart, per HIV-infected subject; one DXA per uninfected subject; X-ray at same time as DXA unless subject Tanner Stage 5 ] [ Designated as safety issue: No ]
    Assessed via DXA scan and x-ray for bone age; subjects meeting the BMD trigger based on the DXA also have the following laboratory assessments: TSH, calcium, 25-hydroxy-vitamin D, bone-specific alkaline, N-terminal telopeptide of type I collagen phosphatase, and PTH in real time and repository specimens for assay of pro-inflammatory cytokines (IL-1, IL-6, TNF-a)

  • Dyslipidemia [ Time Frame: Annually for 10 years ] [ Designated as safety issue: No ]
    Assessed via lipid testing; subjects meeting the metabolic trigger based on the results of the lipid tests also have the following measurements: endothelial dysfunction (I, E, P-selectins: V, I-CAM-1, endothelin-1, hs-CRP, homocysteine, apolipoprotein B, lipoprotein (a), and vWF antigen)

  • Cardiac abnormalities [ Time Frame: Measured once per subject until study reached 400 echocardiograms ] [ Designated as safety issue: No ]
    Assessed through the administration of echocardiograms and serum biomarkers (ProBNP)

  • Hearing dysfunction [ Time Frame: Once per subject. ] [ Designated as safety issue: No ]
    Assessed via audiologic evaluation conducted by an audiologist.

  • Language dysfunction [ Time Frame: Annually for 10 years ] [ Designated as safety issue: No ]
    Assessed using the Woodcock and CELF IV language tests

  • Neurodevelopmental abnormalities [ Time Frame: Annually for 10 years ] [ Designated as safety issue: No ]
    Assessed via the following neurodevelopmental tests: WISC IV, WAIS IV, BRIEF, Children's Color Trails Test, Trail Making Tests, WIAT-II screen, ABAS, Parent Child Relationship Inventory, BASC-2, Quality of Life Interview, Stressful Life Events Questionnaire, Monitoring the Future

  • Substance Use [ Time Frame: Annually starting at a minimum of 10 years of age for 10 years ] [ Designated as safety issue: No ]
    The assessment of sexual activity is conducted using an Audio Computer Assisted Survey Instrument (ACASI). ACASI uses computer and voice recordings so that the participant hears (through headphones) and sees (on the screen) each question and response list. The use of ACASI is proven to minimize response bias due to the presence of an interviewer.

  • Sexual Activity [ Time Frame: Annually starting at a minimum of 10 years of age for 10 years ] [ Designated as safety issue: No ]
    The assessment of substance use is conducted using an Audio Computer Assisted Survey Instrument (ACASI). ACASI uses computer and voice recordings so that the participant hears (through headphones) and sees (on the screen) each question and response list. The use of ACASI is proven to minimize response bias due to the presence of an interviewer.

  • Pregnancy [ Time Frame: Annually for 10 years ] [ Designated as safety issue: No ]
    Assessed via medical record review to record incidents of pregnancy

  • Sexually Transmitted Infection [ Time Frame: Annually for 10 years ] [ Designated as safety issue: No ]
    Assessed via medical record review to record results of clinically conducted STI and Pap testing and pelvic exams

  • Mitochondrial dysfunction [ Time Frame: Annually for 10 years ] [ Designated as safety issue: No ]
    Assessed via measurement of serum lactate levels, OXPHO immunoassays, mitochondrial specific oxidative stress, mtDNA copies/cell, mrRNA transcripts

  • Lactic acidosis [ Time Frame: Annually for 10 years ] [ Designated as safety issue: No ]
    Assessed through the measurement of blood lactate levels using a point-of-care lactate measuring device; a single venous lactate measurement will be conducted in cases where the POC lactate measure is elevated

  • Renal abnormalities [ Time Frame: Annually for 10 years ] [ Designated as safety issue: No ]
    Assessed through the following laboratory measurements: chemistry panel, urinalysis, protein/creatinine ratio, dip stick urine test


Biospecimen Retention:   Samples With DNA

Serum, cell pellets, plasma, saliva, and urine


Enrollment: 678
Study Start Date: March 2007
Estimated Study Completion Date: July 2020
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
Groups/Cohorts
Infected Cohort
Perinatally HIV-infected adolescents from 7 years of age (7th birthday) up to but not including the 16th birthday at enrollment, engaged in care with ART treatment history available.
Uninfected Cohort
HIV-uninfected adolescents from 7 years of age (7th birthday) up to but not including the 16th birthday at enrollment born to HIV-infected mothers.

Detailed Description:

The primary objectives of AMP are:

  1. To define the impact of HIV infection and ART on growth and pubertal development (and their hormonal regulation), along with the cognitive, academic, and social development, of pre-adolescents and adolescents with perinatal HIV infection as they move through adolescence into adulthood.
  2. To identify infectious and non-infectious complications of HIV disease, including the toxicities of antiretroviral therapy (ART).
  3. To investigate:

    • Cognitive and behavioral changes over time, including medication adherence, family and social function, and high risk behaviors such as risky sexual behavior, licit and illicit drug use, and alcohol use;
    • Changes in language and hearing;
    • Changes in glucose metabolism, body composition, and bone mineralization;
    • Changes in lipid metabolism and other risk factors for cardiovascular disease;
    • Risk factors for secondary transmission of HIV; and
    • The occurrence and clinical course of cervical HPV infections among females.

The domain-specific aims of AMP are:

  1. Growth and sexual maturation: To longitudinally track growth and sexual maturation and the factors that influence growth and maturation in HIV-infected children when compared to HIV-exposed but uninfected children.
  2. Metabolic risk factors for cardiovascular disease: To characterize the emergence of abnormal glucose metabolism, lipid abnormalities, body composition and other risk factors for cardiovascular disease and identify the contributing influences in HIV-infected children when compared to HIV-exposed but uninfected children.
  3. Cardiac function: To estimate the prevalence of cardiac structural and functional abnormalities in HIV-infected children and youth when compared to HIV-exposed but uninfected children.
  4. Bone mineral density: To estimate the differences in bone mineral density of HIV-infected children when compared to HIV-exposed but uninfected children and to identify factors contributing to abnormal bone mineralization.
  5. Neurologic, neurodevelopment, language, and behavioral function:

    • To examine cognitive and behavioral outcomes of HIV-infected children and adolescents, including high risk behaviors such as risky sexual behavior, licit and illicit drug use, and alcohol use, neurodevelopmental impairment, school achievement and to compare them with an HIV-exposed but uninfected control cohort.
    • To examine non-adherence to antiretroviral therapy and predictors of non-adherence among HIV-infected children receiving ART.
    • To examine family and psychosocial factors associated with emotional and behavioral problems.
  6. Adolescent gynecology and STI infection:

    • To evaluate the incidence of and risk factors for acquiring STIs/vaginal infections (C. trachomatis, N. gonorrhea, T. vaginalis, syphilis, genital warts, HPV, and HSV) for males and females, and in addition bacterial vaginosis for females.
    • To evaluate the incidence, predictors, and outcomes of pregnancy.
  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

HIV-infected and -uninfected children from 7 years of age (7th birthday) up to but not including the 16th birthday at the time of enrollment born to HIV-infected mothers. Participants will be children previously enrolled in any of the studies included on the list of approved studies for co-enrollment into AMP noted above, or another study with Protocol Team approval or has medical record documentation since birth of key medical data related to their HIV infection.

Criteria

HIV-Infected Cohort

Inclusion Criteria:

  • Perinatal HIV infection as documented in the medical record.
  • Age 7 years (7th birthday) up to but not including the 16th birthday at enrollment.
  • Engaged in care and ART history is available.
  • Either: Previous or current enrollment in any of the studies included on the list of approved studies allowing for enrollment into AMP. Children participating in other studies may be enrolled with approval of the Protocol Team. Additional approved protocols will be listed on the PHACS website; Or: Available medical record documentation since birth of 1)ART exposure history 2)Opportunistic Infection (OI) prophylaxis exposure history 3) Viral load and CD4 count history and 4) Major medical events history
  • Willingness to participate and provide parental/legal guardian permission with assent. Children who do not know their HIV infection status will not be excluded.

Exclusion criteria: HIV acquired by other than maternal-child transmission (e.g., blood products, sexual contact, and IV drug use) as documented in the medical record.

HIV-Uninfected, HIV-Exposed Control Cohort

Inclusion criteria:

  • HIV-uninfected and born to an HIV-infected mother as documented in the medical record.
  • Age 7 years (7th birthday) up to but not including the 16th birthday at enrollment.
  • Previous or current enrollment in any of the studies included on the list of approved studies allowing for enrollment into AMP. Children participating in other studies may be enrolled with approval of the Protocol Team. Additional approved protocols will be listed on the PHACS website; Or: Available medical record documentation since birth of 1)ART exposure history and 2) Major medical events history.
  • Willingness to participate and provide parental/legal guardian permission with assent.

Exclusion Criteria: None.

  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: NCT01418014

Locations
United States, California
University of California San Diego
La Jolla, California, United States, 92093
United States, Colorado
University of Colorado Denver Health Sciences Center
Aurora, Colorado, United States, 80045
United States, Florida
Children's Diagnostic and Treatment Center
Fort Lauderdale, Florida, United States, 33316
University of Miami
Miami, Florida, United States, 33136
United States, Illinois
Ann and Robert H. Lurie Children's Hospital
Chicago, Illinois, United States, 60614
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, New Jersey
Rutgers - New Jersey Medical School
Newark, New Jersey, United States, 07101
United States, New York
Bronx Lebanon Hospital Center
Bronx, New York, United States, 10457
Jacobi Medical Center
Bronx, New York, United States, 10461
United States, Pennsylvania
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Puerto Rico
San Juan Research Hospital
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
Harvard School of Public Health
Tulane University School of Medicine
NIH Office of AIDS Research (OAR)
Investigators
Principal Investigator: George R Seage III, ScD, MPH Harvard School of Public Health
Principal Investigator: Russell Van Dyke, M.D. Tulane University School of Medicine
  More Information

Additional Information:
Publications:
Miller TI, Borkowsky W, DiMeglio LA, Dooley L, Geffner ME, Hazra R, McFarland EJ, Mendez AJ, Patel K, Siberry GK, Van Dyke RB, Worrell CJ, Jacobson DL; Pediatric HIV/AIDS Cohort Study (PHACS), Shearer W, Cooper N, Harris L, Purswani M, Baig M, Cintron A, Puga A, Navarro S, Patton D, Burchett S, Karthas N, Kammerer B, Yogev R, Malee K, Hunter S, Cagwin E, Wiznia A, Burey M, Nozyce M, Chen J, Gobs E, Grant M, Knapp K, Allison K, Garvie P, Acevedo-Flores M, Rios H, Olivera V, Silio M, Borne C, Sirois P, Spector S, Norris K, Nichols S, McFarland E, Barr E, Chambers C, Watson D, Messenger N, Belanger R, Dieudonne A, Bettica L, Adubato S, Scott G, Himic L, Willen E. Metabolic abnormalities and viral replication are associated with biomarkers of vascular dysfunction in HIV-infected children. HIV Med. 2012 May;13(5):264-75. doi: 10.1111/j.1468-1293.2011.00970.x. Epub 2011 Dec 4.

Responsible Party: George Seage, Professor of Epidemiology, Harvard School of Public Health
ClinicalTrials.gov Identifier: NCT01418014     History of Changes
Other Study ID Numbers: HD052102 - PH200, PH200
Study First Received: July 22, 2011
Last Updated: October 17, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

ClinicalTrials.gov processed this record on October 23, 2014