Childhood Asthma Management Program (CAMP) Phases I (Trial), II (CAMPCS), III (CAMPCS/2), and IV (CAMPCS/3)

Asthma Clinical Trial

— CAMP  

Official title:

Childhood Asthma Management Program

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000575
• Other study ID #: 213
• Secondary ID: 5U01HL075417
• Status: Completed
• Phase: Phase 3
• First received: October 27, 1999
• Last updated: February 20, 2014
• Start date: September 1991
• Est. completion date: March 2012

Study information

• Verified date: February 2014
• Source: Johns Hopkins Bloomberg School of Public Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the long term effects of anti-inflammatory therapy compared to bronchodilator therapy on the course of asthma, particularly on lung function and bronchial hyperresponsiveness, and on physical and psychosocial growth and development.

Description:

BACKGROUND:

Asthma is a serious chronic condition, affecting approximately 14 million Americans. People with asthma experience well over 100 million days of restricted activity annually, and costs for asthma care exceed $10 billion a year. Asthma is much more prevalent among children than adults.

Hospitalizations for asthma have been increasing among children. For example, from 1979 to 1987, the hospital discharge rate with asthma as the first-listed diagnosis rose 43 percent among children less than 15 years of age, from 19.8 to 28.4 discharges per 10,000 population.

Death rates for asthma are greater in Blacks than in whites, and the difference is increasing. In 1979, Blacks of both sexes were about twice as likely to die from asthma as whites. Over the past decade this ratio has increased, and by 1987 the asthma death rate was almost three times greater among Blacks than whites. In children, these mortality differences between Blacks and whites are even more striking.

Current knowledge about the epidemiology and natural history of childhood asthma is incomplete, but the relationship between asthma early in life and development of chronic obstructive pulmonary disease (COPD) in adulthood is becoming more apparent. Asthmatic children with persistent and severe asthma symptoms have lower levels of lung function by young adulthood than those with milder disease. Recent longitudinal studies have confirmed a decrease in rate of growth of lung function as measured by FEV1 among symptomatic (primarily wheeze) children compared to asymptomatic children. Among persons who develop COPD, initial level of lung function is the strongest predictor of subsequent rapid decline of ventilatory function.

Thus, less than maximally attained levels of lung function among children with asthma may predispose them to greater than normal decline of lung function later in life. Although the long-term effect of treatment on the course of asthma is not known, the treatment goal of decreasing bronchial hyperresponsiveness and maximizing lung function and growth during childhood may have a beneficial effect on lung health throughout life and prevent progression to irreversible airflow obstruction.

Two classes of medications are currently available for treatment of inflammation--corticosteroids and cromolyn sodium. Inhaled corticosteroids have significantly fewer side effects than systemic administration. Corticosteroids do not inhibit the early asthmatic response, but are effective in suppressing the inflammation and bronchial hyperresponsiveness of the late phase response. Long-term studies of inhaled corticosteroids have shown beneficial effects on lung function as measured by FEV1. However, there has been concern about possible effects of long-term use of inhaled corticosteroids. Although epidemiological studies of the use of inhaled corticosteroids have shown no significant adverse effects, large-scale randomized controlled studies of their effects on children's growth and development are needed.

When CAMP was initiated in the United States, bronchodilator treatment was the most common approach to therapy. Two classes of bronchodilators, inhaled beta-2-adrenergic agonists and oral theophylline, are most frequently prescribed for asthma. To date, no randomized, controlled studies have compared the two classes of anti-inflammatory medications to each other and to bronchodilator therapy on the course of asthma.

The initiative was proposed by the Pulmonary Disease Advisory Committee working group in October 1987 and approved by the full committee at the February 1988 meeting and by the National Heart, Lung, and Blood Advisory Council in May 1990. The Request for Proposals was released in October 1990. Awards were made in September 1991.

DESIGN NARRATIVE:

Children were randomized to one of three treatment groups to receive either: inhaled albuterol alone, albuterol with inhaled budesonide, albuterol with nedocromil. Upon randomization, data were collected on demographic factors, physical and psychosocial development, clinical factors including medical history and extent of allergies, and quality of life factors including limitation of activity, absenteeism from school, emergency room visits, and hospitalizations. All subjects received a common educational program, differing only in the information presented regarding the medication used by the subjects. Each subject was given a standard protocol for dealing with asthma attacks. All subjects were treated and followed for five years with quarterly visits yearly. Recruitment began in July 1993 and ended in June 1995 with the accrual of 1,041 subjects.

The study has been extended through June 2011 through three funding phases to observe the subjects but not provide asthma treatment. This will allow CAMP to (1.) determine the full impact of 4 to 6 years of anti-inflammatory therapy on attaining maximal lung function and final height; (2.) examine the natural history of asthma through age 26; and (3.) define patterns of reduced lung function growth and early decline of lung function in young adults.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1041
• Est. completion date: March 2012
• Est. primary completion date: October 1999
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 12 Years

Eligibility

Inclusion criteria:

• Age 5 to 12 years at time of screening

• Chronic asthma as evidenced by one or more of the following historical findings for at least 6 months during the past year:

• Asthma symptoms at least 2 times per week

• 2 or more usages per week of an inhaled bronchodilator

• Daily asthma medication

• Current asthma symptoms either by diary symptom code of 1 or greater or am or pm PEFR less than 80% of personal best post-bronchodilator value by diary, on 8 or more days during the prn screening period

• Methacholine sensitivity: estimated PC20 FEV1 less than or equal to 12.5 mg/ml

• Consent of guardian and assent of child

• Ability to comply with trial for 5 - 6.5 years

Exclusion criteria:

• Presence of one or more of the following confounding or complicating problems:

• Any other active pulmonary disease

• Any chronic condition presumed to interfere with the successful completion of the project or confound its interpretation

• Pulmonary function testing findings suggesting a ventilatory defect other than asthma, or evidence of existing irreversible lung damage

• Severe chronic sinusitis or nasal polyposis

• Introduction of or a change in allergen immunotherapy within the past month

• Use of more than 4 sprays of nasal steroids daily (only beclomethasone allowed)

• Pregnancy

• Current use of metoclopramide, ranitidine, or cimetidine

• Treatment for gastroesophageal reflux

• Participation in another drug study

• Evidence of severe asthma as indicated by one or more of the following:

• Two or more hospitalizations for asthma in the past year

• Six or more steroid bursts in the past year

• Demonstrated need for continuous use of glucocorticoids, either oral or inhaled

• When off inhaled O2-agonist for more than 4 hrs and theophylline for more than 24 hrs, FEV1 less than 65% predicted

• Intubation for asthma at any time in the past

• Need for 9 or more puffs/day of albuterol for each of 3 consecutive days (excluding preventive use prior to exercise), or nocturnal asthma awakenings more than 1.5 times per week on average, or average diary card symptom code greater than 2, or requirement for other medications to control asthma, during prn screening period

• Inability to perform 3 acceptable FVC maneuvers of which at least 2 reproducible FEV1s are within 10% of the largest FEV1

• Inability to complete the methacholine challenge or methacholine PC20 FEV1 greater than 12.5 mg/ml

• Evidence that patient or family may be unreliable or non-compliant or may move from the metropolitan area before trial completion

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma
• Lung Diseases

Intervention

Drug:
• Placebo
Two 100 Og puffs budesonide placebo bid + two 90 Og puffs albuterol prn OR four 2 mg puffs nedocromil placebo bid + two 90 Og puffs albuterol prn.
• Nedocromil
Four 2 mg puffs bid + two 90 Og puffs albuterol prn
• Budesonide
Two 100 Og puffs bid + two 90 Og puffs albuterol prn.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins Bloomberg School of Public Health	CAMP Steering Committee, National Heart, Lung, and Blood Institute (NHLBI)

References & Publications (37)

Annett RD, Aylward EH, Lapidus J, Bender BG, DuHamel T. Neurocognitive functioning in children with mild and moderate asthma in the childhood asthma management program. The Childhood Asthma Management Program (CAMP) Research Group. J Allergy Clin Immunol. 2000 Apr;105(4):717-24. — View Citation

Annett RD, Bender BG, Lapidus J, Duhamel TR, Lincoln A. Predicting children's quality of life in an asthma clinical trial: what do children's reports tell us? J Pediatr. 2001 Dec;139(6):854-61. — View Citation

Annett RD, Stansbury K, Kelly HW, Strunk RC. Association of hypothalamic-pituitary-adrenal axis function with neuropsychological performance in children with mild/moderate asthma. Child Neuropsychol. 2005 Aug;11(4):333-48. — View Citation

Bacharier LB, Dawson C, Bloomberg GR, Bender B, Wilson L, Strunk RC; Childhood Asthma Management Program Research Group. Hospitalization for asthma: atopic, pulmonary function, and psychological correlates among participants in the Childhood Asthma Management Program. Pediatrics. 2003 Aug;112(2):e85-92. — View Citation

Bacharier LB, Raissy HH, Wilson L, McWilliams B, Strunk RC, Kelly HW. Long-term effect of budesonide on hypothalamic-pituitary-adrenal axis function in children with mild to moderate asthma. Pediatrics. 2004 Jun;113(6):1693-9. — View Citation

Bender BG, Annett RD, Iklé D, DuHamel TR, Rand C, Strunk RC. Relationship between disease and psychological adaptation in children in the Childhood Asthma Management Program and their families. CAMP Research Group. Arch Pediatr Adolesc Med. 2000 Jul;154(7):706-13. — View Citation

Bender BG, Ellison MC, Gleason M, Murphy JR, Sundstrom DA, Szefler SJ. Minimizing attrition in a long-term clinical trial of pediatric asthma. Ann Allergy Asthma Immunol. 2003 Aug;91(2):168-76. — View Citation

Covar RA, Spahn JD, Martin RJ, Silkoff PE, Sundstrom DA, Murphy J, Szefler SJ. Safety and application of induced sputum analysis in childhood asthma. J Allergy Clin Immunol. 2004 Sep;114(3):575-82. — View Citation

Covar RA, Spahn JD, Murphy JR, Szefler SJ; Childhood Asthma Management Program Research Group. Progression of asthma measured by lung function in the childhood asthma management program. Am J Respir Crit Care Med. 2004 Aug 1;170(3):234-41. Epub 2004 Mar 17. — View Citation

Covar RA, Szefler SJ, Martin RJ, Sundstrom DA, Silkoff PE, Murphy J, Young DA, Spahn JD. Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma. J Pediatr. 2003 May;142(5):469-75. — View Citation

DeMeo DL, Lange C, Silverman EK, Senter JM, Drazen JM, Barth MJ, Laird N, Weiss ST. Univariate and multivariate family-based association analysis of the IL-13 ARG130GLN polymorphism in the Childhood Asthma Management Program. Genet Epidemiol. 2002 Nov;23(4):335-48. — View Citation

Design and implementation of a patient education center for the Childhood Asthma Management Program. Childhood Asthma Management Program Research Group. Ann Allergy Asthma Immunol. 1998 Dec;81(6):571-81. — View Citation

Huss K, Adkinson NF Jr, Eggleston PA, Dawson C, Van Natta ML, Hamilton RG. House dust mite and cockroach exposure are strong risk factors for positive allergy skin test responses in the Childhood Asthma Management Program. J Allergy Clin Immunol. 2001 Jan;107(1):48-54. — View Citation

Kelly HW, Strunk RC, Donithan M, Bloomberg GR, McWilliams BC, Szefler S; Childhood Asthma Management Program (CAMP). Growth and bone density in children with mild-moderate asthma: a cross-sectional study in children entering the Childhood Asthma Management Program (CAMP). J Pediatr. 2003 Mar;142(3):286-91. — View Citation

Lake SL, Lyon H, Tantisira K, Silverman EK, Weiss ST, Laird NM, Schaid DJ. Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. Hum Hered. 2003;55(1):56-65. — View Citation

Lange C, Lyon H, DeMeo D, Raby B, Silverman EK, Weiss ST. A new powerful non-parametric two-stage approach for testing multiple phenotypes in family-based association studies. Hum Hered. 2003;56(1-3):10-7. — View Citation

Larsen GL. Focusing on childhood asthma: the childhood asthma management program (CAMP). J Allergy Clin Immunol. 1999 Mar;103(3 Pt 1):371-3. — View Citation

Lazarus R, Raby BA, Lange C, Silverman EK, Kwiatkowski DJ, Vercelli D, Klimecki WJ, Martinez FD, Weiss ST. TOLL-like receptor 10 genetic variation is associated with asthma in two independent samples. Am J Respir Crit Care Med. 2004 Sep 15;170(6):594-600. Epub 2004 Jun 16. — View Citation

Long-term effects of budesonide or nedocromil in children with asthma. The Childhood Asthma Management Program Research Group. N Engl J Med. 2000 Oct 12;343(15):1054-63. — View Citation

Nelson HS, Szefler SJ, Jacobs J, Huss K, Shapiro G, Sternberg AL. The relationships among environmental allergen sensitization, allergen exposure, pulmonary function, and bronchial hyperresponsiveness in the Childhood Asthma Management Program. J Allergy Clin Immunol. 1999 Oct;104(4 Pt 1):775-85. — View Citation

Raby BA, Hwang ES, Van Steen K, Tantisira K, Peng S, Litonjua A, Lazarus R, Giallourakis C, Rioux JD, Sparrow D, Silverman EK, Glimcher LH, Weiss ST. T-bet polymorphisms are associated with asthma and airway hyperresponsiveness. Am J Respir Crit Care Med. 2006 Jan 1;173(1):64-70. Epub 2005 Sep 22. — View Citation

Raby BA, Silverman EK, Lazarus R, Lange C, Kwiatkowski DJ, Weiss ST. Chromosome 12q harbors multiple genetic loci related to asthma and asthma-related phenotypes. Hum Mol Genet. 2003 Aug 15;12(16):1973-9. — View Citation

Raby BA, Van Steen K, Celedón JC, Litonjua AA, Lange C, Weiss ST; CAMP Research Group. Paternal history of asthma and airway responsiveness in children with asthma. Am J Respir Crit Care Med. 2005 Sep 1;172(5):552-8. Epub 2005 Jun 3. — View Citation

Randolph AG, Lange C, Silverman EK, Lazarus R, Silverman ES, Raby B, Brown A, Ozonoff A, Richter B, Weiss ST. The IL12B gene is associated with asthma. Am J Hum Genet. 2004 Oct;75(4):709-15. Epub 2004 Aug 20. — View Citation

Randolph AG, Lange C, Silverman EK, Lazarus R, Weiss ST. Extended haplotype in the tumor necrosis factor gene cluster is associated with asthma and asthma-related phenotypes. Am J Respir Crit Care Med. 2005 Sep 15;172(6):687-92. Epub 2005 Jun 23. — View Citation

Recruitment of participants in the childhood Asthma Management Program (CAMP). I. Description of methods: Childhood Asthma Management Program Research Group. J Asthma. 1999 May;36(3):217-37. — View Citation

Silverman EK, Kwiatkowski DJ, Sylvia JS, Lazarus R, Drazen JM, Lange C, Laird NM, Weiss ST. Family-based association analysis of beta2-adrenergic receptor polymorphisms in the childhood asthma management program. J Allergy Clin Immunol. 2003 Nov;112(5):870-6. — View Citation

Slaughter JC, Lumley T, Sheppard L, Koenig JQ, Shapiro GG. Effects of ambient air pollution on symptom severity and medication use in children with asthma. Ann Allergy Asthma Immunol. 2003 Oct;91(4):346-53. — View Citation

Strunk RC, Bender B, Young DA, Sagel S, Glynn E, Caesar M, Lawhon C. Predictors of protocol adherence in a pediatric asthma clinical trial. J Allergy Clin Immunol. 2002 Oct;110(4):596-602. — View Citation

Strunk RC, Sternberg AL, Bacharier LB, Szefler SJ. Nocturnal awakening caused by asthma in children with mild-to-moderate asthma in the childhood asthma management program. J Allergy Clin Immunol. 2002 Sep;110(3):395-403. — View Citation

Tantisira KG, Lake S, Silverman ES, Palmer LJ, Lazarus R, Silverman EK, Liggett SB, Gelfand EW, Rosenwasser LJ, Richter B, Israel E, Wechsler M, Gabriel S, Altshuler D, Lander E, Drazen J, Weiss ST. Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids. Hum Mol Genet. 2004 Jul 1;13(13):1353-9. Epub 2004 May 5. — View Citation

Tantisira KG, Litonjua AA, Weiss ST, Fuhlbrigge AL; Childhood Asthma Management Program Research Group. Association of body mass with pulmonary function in the Childhood Asthma Management Program (CAMP). Thorax. 2003 Dec;58(12):1036-41. — View Citation

The Childhood Asthma Management Program (CAMP): design, rationale, and methods. Childhood Asthma Management Program Research Group. Control Clin Trials. 1999 Feb;20(1):91-120. — View Citation

Weiss ST, Horner A, Shapiro G, Sternberg AL; Childhood Asthma Management Program (CAMP) Research Group. The prevalence of environmental exposure to perceived asthma triggers in children with mild-to-moderate asthma: data from the Childhood Asthma Management Program (CAMP). J Allergy Clin Immunol. 2001 Apr;107(4):634-40. — View Citation

Weiss ST, Van Natta ML, Zeiger RS. Relationship between increased airway responsiveness and asthma severity in the childhood asthma management program. Am J Respir Crit Care Med. 2000 Jul;162(1):50-6. — View Citation

Yu O, Sheppard L, Lumley T, Koenig JQ, Shapiro GG. Effects of ambient air pollution on symptoms of asthma in Seattle-area children enrolled in the CAMP study. Environ Health Perspect. 2000 Dec;108(12):1209-14. — View Citation

Zeiger RS, Dawson C, Weiss S. Relationships between duration of asthma and asthma severity among children in the Childhood Asthma Management Program (CAMP). J Allergy Clin Immunol. 1999 Mar;103(3 Pt 1):376-87. — View Citation

* Note: There are 37 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary Function as Measured by Normalized FEV1 Over a 4-6 Year Period	Change in FEV1 % of predicted, post-bronchodilator use, from baseline to the end of treatment (4-6 years after randomization). Percent predicted determined from three separate published sets of reference equations for white, black, and Hispanic children - see NEJM 343: 1054-1062, 2000 for more details and references.	At the end of treatment, 4-6 years from baseline assessment	No
Secondary	Bronchial Responsiveness to Serial Methacholine Concentrations Inhaled Into the Lungs	Bronchial responsiveness to serial concentrations of inhaled methacholine solution (mg/ml) as measured by serial ratios of follow-up to baseline FEV1 (forced volume of air expired from the lungs in one second). A dose-response curve is calculated from the serial ratios in relation to the serial concentrations to determine PC20, the concentration associated with a 20% drop from baseline in FEV1; this PC20 is the outcome measure with units mg/ml of methacholine.	4-6 years from baseline	No
Secondary	Change From Baseline in the Rate of Asthma Free Days	Change from baseline proportion of days without asthma symptoms or other asthma related events to proportion of days during the 4-6 years of follow-up. Asthma free days were determined from daily asthma diaries kept from baseline to the end of treatment, 4-6 years later.	4-6 years from baseline	No
Secondary	Need for Urgent Care for Asthma	Counts during the period of treatment (4-6 years) of visits to emergency rooms or equivalent urgent care settings for asthma treatment.	4-6 years from baseline	No
Secondary	Mortality	Counts of deaths from asthma.	4-6 years from baseline	Yes
Secondary	Change in Height From Baseline to End of Treatment, 4-6 Years Later	Change in standing height from baseline to end of treatment. Standing height is measured three times without shoes using a calibrated Harpenden stadiometer; the average of the three repeated heights to the nearest 0.1 cm is the height measure at either baseline or end of treatment.	4-6 years from baseline	No
Secondary	Standardized Depression Scale -- Children's Depression Inventory	Change in total score on the Children's Depression Inventory from baseline to the end of treatment, 4-6 years later. The total score ranges from 0-54 with higher scores indicating greater levels of depression.	4-6 years from baseline	No