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AMP: Adolescent Master Protocol

Sponsor
Harvard School of Public Health (HSPH) (Other)
Overall Status
Completed
CT.gov ID
NCT01418014
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), National Institute on Drug Abuse (NIDA) (NIH), National Institute of Allergy and Infectious Diseases (NIAID) (NIH), National Institute of Mental Health (NIMH) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Institute on Deafness and Other Communication Disorders (NIDCD) (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH), National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Tulane University School of Medicine (Other), National Institute of Dental and Craniofacial Research (NIDCR) (NIH), NIH Office of AIDS Research (OAR) (NIH)
678
Enrollment
15
Locations
167.1
Actual Duration (Months)
45.2
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase

    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.

    1. 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 Design

    Study Type:
    Observational
    Actual Enrollment :
    678 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Adolescent Master Protocol
    Actual Study Start Date :
    Mar 1, 2007
    Actual Primary Completion Date :
    Feb 1, 2021
    Actual Study Completion Date :
    Feb 1, 2021

    Arms and Interventions

    Arm Intervention/Treatment
    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.

    Outcome Measures

    Primary Outcome Measures

    1. Abnormal growth [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.

    2. Delayed sexual maturation [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

    3. Abnormal bone mineral density [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)

    4. Dyslipidemia [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)

    5. Cardiac abnormalities [Measured once per subject until study reached 400 echocardiograms]

      Assessed through the administration of echocardiograms and serum biomarkers (ProBNP)

    6. Hearing dysfunction [Once per subject.]

      Assessed via audiologic evaluation conducted by an audiologist.

    7. Language dysfunction [Annually for 10 years]

      Assessed using the Woodcock and CELF IV language tests

    8. Neurodevelopmental abnormalities [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

    9. Substance Use [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.

    10. Sexual Activity [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.

    11. Pregnancy [Annually for 10 years]

      Assessed via medical record review to record incidents of pregnancy

    12. Sexually Transmitted Infection [Annually for 10 years]

      Assessed via medical record review to record results of clinically conducted STI and Pap testing and pelvic exams

    13. Mitochondrial dysfunction [Annually for 10 years]

      Assessed via measurement of serum lactate levels, OXPHO immunoassays, mitochondrial specific oxidative stress, mtDNA copies/cell, mrRNA transcripts

    14. Lactic acidosis [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

    15. Renal abnormalities [Annually for 10 years]

      Assessed through the following laboratory measurements: chemistry panel, urinalysis, protein/creatinine ratio, dip stick urine test

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    7 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    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

    Locations

    Site City State Country Postal Code
    1 University of California San Diego La Jolla California United States 92093
    2 University of Colorado Denver Health Sciences Center Aurora Colorado United States 80045
    3 Children's Diagnostic and Treatment Center Fort Lauderdale Florida United States 33316
    4 University of Miami Miami Florida United States 33136
    5 Ann and Robert H. Lurie Children's Hospital Chicago Illinois United States 60614
    6 Tulane University Health Sciences Center New Orleans Louisiana United States 70112
    7 University of Maryland Baltimore Maryland United States 21201
    8 Children's Hospital Boston Boston Massachusetts United States 02115
    9 Rutgers - New Jersey Medical School Newark New Jersey United States 07101
    10 Bronx Lebanon Hospital Center Bronx New York United States 10457
    11 Jacobi Medical Center Bronx New York United States 10461
    12 St. Christopher's Hospital for Children Philadelphia Pennsylvania United States 19134
    13 St. Jude Children's Research Hospital Memphis Tennessee United States 38105
    14 Baylor College of Medicine Houston Texas United States 77030
    15 San Juan Research Hospital San Juan Puerto Rico 00936

    Sponsors and Collaborators

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

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Paige Williams, Senior Lecturer on Biostatistics, Harvard School of Public Health (HSPH)
    ClinicalTrials.gov Identifier:
    NCT01418014
    Other Study ID Numbers:
    • HD052102 - PH200
    • PH200
    First Posted:
    Aug 16, 2011
    Last Update Posted:
    Aug 27, 2021
    Last Verified:
    Aug 1, 2021
    Additional relevant MeSH terms:
    Acquired Immunodeficiency Syndrome
    HIV Infections

    Study Results

    No Results Posted as of Aug 27, 2021