Intractable gastroesophageal reflux disease (GERD) in children with cerebral palsy (CP) and other development disabilities is prevalent and difficult to control. It carries a high morbidity with frequent hospitalizations. Proton pump inhibitors (PPIs), the mainstay of therapy for GERD, have a high failure rate in children with CP, presumably because they do not affect the rate of transient lower esophageal sphincter relaxations (TLESRs) and do not control or may increase the presence of non-acid reflux. The recent emergence of multichannel intraluminal impedance (MII) monitoring has revealed that 33-74% of reflux in otherwise healthy children and children with CP is non-acidic. However in children with CP, fundoplication is associated with twice the complication rate, a higher mortality, three times the morbidity, and four times the re-operation rate, as compared with otherwise healthy patients with GERD. Identifying novel medical therapies that specifically target TLESRs, and therefore decrease both acid and non-acid reflux, are urgently needed. Baclofen, a gamma-amino butyric acid (GABA) agonist used in children with CP to treat spasticity, has been shown in animals and humans to decrease TLESRs and may be effective in treating GERD. This will be a randomized, placebo, controlled study of baclofen to treat intractable GERD in children with CP.
The aims of the study will be to: A) Gain preliminary evidence of the efficacy of baclofen to treat symptoms of GERD, in comparison with placebo, administered for two weeks in children with CP and intractable GERD , b) Assess the efficacy baclofen versus placebo in reducing the number of reflux events detected by MII, c) Assess the efficacy of baclofen versus placebo in reducing the number of total TLESRs and reflux secondary to TLESRs detected by esophageal function testing (EFT) and d) Assess the safety and tolerability of baclofen administered over two weeks to treat children with CP and intractable GERD. Children 3 to 18 years old will be eligible. After inclusion they will have a 2 week observation period, followed by a 36 hour admission to the GCRC for an EFT and MII with videorecording. Patients will then be randomized to baclofen or placebo. They will return for evaluation after completing 2 weeks of therapy, and will be readmitted for repeat EFT and MII while on baclofen therapy. The present study could have a major impact on the treatment of children with CP and intractable GERD by providing a new therapy and an alternative to surgery. This study will provide evidence about the efficacy and safety of baclofen for the treatment of intractable gastroesophageal relfux disease (GERD), and may represent a new treatment. This study will serve as a basis to test the medication in otherwise healthy children with GERD. ? ? ?
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