Adolescent Master Protocol (AMP)

November 9, 2023 updated by: Paige Williams, Harvard School of Public Health (HSPH)

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).

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

678

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00936
        • San Juan Research Hospital
  • United States
    • California
      • La Jolla, California, United States, 92093
        • University of California San Diego
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Denver Health Sciences Center
    • Florida
      • Fort Lauderdale, Florida, United States, 33316
        • Children's Diagnostic and Treatment Center
      • Miami, Florida, United States, 33136
        • University of Miami
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Ann and Robert H. Lurie Children's Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Health Sciences Center
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital Boston
    • New Jersey
      • Newark, New Jersey, United States, 07101
        • Rutgers - New Jersey Medical School
    • New York
      • Bronx, New York, United States, 10461
        • Jacobi Medical Center
      • Bronx, New York, United States, 10457
        • Bronx Lebanon Hospital Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19134
        • St. Christopher's Hospital for Children
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

7 years and older (Child, Adult, Older Adult)

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 (see below) or has medical record documentation since birth of key medical data related to their HIV infection.

Description

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 as specified in the protocol. Children participating in other studies may be enrolled with approval of the Protocol Team. Additional approved protocols are 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Abnormal growth
Time Frame: Annually for 10 years
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.
Annually for 10 years
Delayed sexual maturation
Time Frame: Annually for 10 years except if subject reaches Tanner Stage 5
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
Annually for 10 years except if subject reaches Tanner Stage 5
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
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)
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
Dyslipidemia
Time Frame: Annually for 10 years
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)
Annually for 10 years
Cardiac abnormalities
Time Frame: Measured once per subject until study reached 400 echocardiograms
Assessed through the administration of echocardiograms and serum biomarkers (ProBNP)
Measured once per subject until study reached 400 echocardiograms
Hearing dysfunction
Time Frame: Once per subject.
Assessed via audiologic evaluation conducted by an audiologist.
Once per subject.
Language dysfunction
Time Frame: Annually for 10 years
Assessed using the Woodcock and CELF IV language tests
Annually for 10 years
Neurodevelopmental abnormalities
Time Frame: Annually for 10 years
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
Annually for 10 years
Substance Use
Time Frame: Annually starting at a minimum of 10 years of age for 10 years
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.
Annually starting at a minimum of 10 years of age for 10 years
Sexual Activity
Time Frame: Annually starting at a minimum of 10 years of age for 10 years
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.
Annually starting at a minimum of 10 years of age for 10 years
Pregnancy
Time Frame: Annually for 10 years
Assessed via medical record review to record incidents of pregnancy
Annually for 10 years
Sexually Transmitted Infection
Time Frame: Annually for 10 years
Assessed via medical record review to record results of clinically conducted STI and Pap testing and pelvic exams
Annually for 10 years
Mitochondrial dysfunction
Time Frame: Annually for 10 years
Assessed via measurement of serum lactate levels, OXPHO immunoassays, mitochondrial specific oxidative stress, mtDNA copies/cell, mrRNA transcripts
Annually for 10 years
Lactic acidosis
Time Frame: Annually for 10 years
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
Annually for 10 years
Renal abnormalities
Time Frame: Annually for 10 years
Assessed through the following laboratory measurements: chemistry panel, urinalysis, protein/creatinine ratio, dip stick urine test
Annually for 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Harvard School of Public Health (HSPH)

Collaborators

National Institute on Drug Abuse (NIDA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Dental and Craniofacial Research (NIDCR)
NIH Office of AIDS Research (OAR)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Tulane University School of Medicine

Investigators

  • Principal Investigator: Russell Van Dyke, M.D., Tulane University School of Medicine
  • Principal Investigator: Paige L Williams, Harvard School of Public Health (HSPH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2007

Primary Completion (Actual)

February 1, 2021

Study Completion (Actual)

February 1, 2021

Study Registration Dates

First Submitted

July 22, 2011

First Submitted That Met QC Criteria

August 15, 2011

First Posted (Estimated)

August 16, 2011

Study Record Updates

Last Update Posted (Estimated)

November 13, 2023

Last Update Submitted That Met QC Criteria

November 9, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HD052102 - PH200
  • PH200 (Other Identifier: PHACS Protocol Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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