Clinical trial NCT01020357: Caffeine for Apnea of Prematurity-Sleep (CAP-S) Study
Official title: Long-Term Effects On Sleep Of Methylxanthine Therapy For Apnea Of Prematurity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Apnea of Prematurity
Keywords: preterm infants
very low birthweight
apnea of prematurity
methylxanthines
sleep disturbance
obstructive sleep apnea syndrome
polysomnography
sleep disruption
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-11-25
Enrollment: 201
Sex: ALL
Minimum age (years): 5
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Apnea of prematurity is a common condition that is usually treated with methylxanthines. Methylxanthines are adenosine receptor blockers that have powerful influences on the central nervous system. However, little is known about the long-term effects of methylxanthines on the developing brain.

The Caffeine for Apnea of Prematurity-Sleep (CAP-S) Study is a sub-study of the main Caffeine for Apnea of Prematurity (CAP) trial, an international placebo-controlled randomized trial of methylxanthine therapy for apnea of prematurity. This sub-study is designed to take advantage of this cohort of ex-premature, 5-7 year old children who were randomized at birth to receive either caffeine or placebo, and are currently receiving detailed neurocognitive and behavioral assessments in the CAP trial.

Detailed description: The use of methylxanthines as therapy for apnea of prematurity may be a double-edged sword. Although widely-used, and efficacious for treatment of apnea of prematurity, long-term drug effects have not been rigorously studied. Neonatal methylxanthine therapy may have long-term impacts on sleep organization and ventilatory control. The CAP trial, funded by the Canadian Institutes of Health Research, was initiated due to the paucity of well-controlled data on the long-term effects of methylxanthines in preterm infants. The initial CAP trial was a multicenter, randomized, placebo-controlled trial of caffeine vs placebo as treatment for apnea of prematurity with follow-up to a corrected age of 18 months. 2,006 infants were enrolled. The CAP trial found that methylxanthines reduced the rates of bronchopulmonary dysplasia (BPD) and cerebral palsy (CP), and did not affect mortality. However, concerns remain regarding long-term sequelae of methylxanthine use. The Canadian Institutes of Health Research have therefore funded further follow-up of the entire CAP trial cohort to age 5 years, corrected for prematurity. The key objectives of this study are to examine the impact of methylxanthines on neurocognition and behavior. This ongoing parent study provides an opportunity to determine potential long-term effects of methylxanthines on sleep disorders, and to correlate these findings with daytime functioning. Our overall hypothesis is that methylxanthine use in preterm infants, while beneficial in the short term, results in longstanding abnormalities in the regulation of sleep, and breathing during sleep.

Eligibility criteria: Inclusion Criteria:

* Males or females aged 5-7 years who are enrolled in the CAP trial.
* Parental/guardian permission (informed consent) and if appropriate, child assent.

Primary outcomes:
measure: Aim 1: The primary outcome is the mean actual sleep time as measured by actigraphy, between subjects who received caffeine vs placebo.
timeFrame: 5-7 years
measure: Aim 2: The primary outcome is the apnea hypopnea index (AHI) between subjects who received caffeine vs placebo.
timeFrame: 5-7 years
measure: Aim 3: The primary outcome is the correlation between full-scale IQ from the Wechsler Preschool and Primary Scale of Intelligence (measured in the CAP trial rather than directly from this protocol), sleep time and AHI.
timeFrame: 5-7 years
Secondary outcomes:
measure: Questionnaire data: National Sleep Foundation (NSF) and Pediatric Sleep Questionnaire (PSQ) scores
timeFrame: 5-7 years
measure: Polysomnography data: Sleep architecture, arousal index, central apnea index, SpO2 and periodic limb movement index.
timeFrame: 5-7 years
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Mercy Hospital for Women
city: Melbourne
country: Australia
facility: Royal Women's Hospital
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: University of Pennsylvania
name: Carole Marcus, M.B.B.Ch.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.
citation: Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med. 2007 Nov 8;357(19):1893-902. doi: 10.1056/NEJMoa073679.
citation: Marcus CL, Meltzer LJ, Roberts RS, Traylor J, Dix J, D'ilario J, Asztalos E, Opie G, Doyle LW, Biggs SN, Nixon GM, Narang I, Bhattacharjee R, Davey M, Horne RS, Cheshire M, Gibbons J, Costantini L, Bradford R, Schmidt B; Caffeine for Apnea of Prematurity-Sleep Study. Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age. Am J Respir Crit Care Med. 2014 Oct 1;190(7):791-9. doi: 10.1164/rccm.201406-1092OC.
citation: Marcus CL, Traylor J, Biggs SN, Roberts RS, Nixon GM, Narang I, Bhattacharjee R, Davey MJ, Horne RS, Cheshire M, Gibbons KJ, Dix J, Asztalos E, Doyle LW, Opie GF, D'ilario J, Costantini L, Bradford R, Schmidt B. Feasibility of comprehensive, unattended ambulatory polysomnography in school-aged children. J Clin Sleep Med. 2014 Aug 15;10(8):913-8. doi: 10.5664/jcsm.3970.