title: The Collaborative Lithium Trials (CoLT): specific aims, methods, and implementation.
abstract: BACKGROUND
  Lithium is a benchmark treatment for bipolar illness in adults. However, there has been relatively little methodologically stringent research regarding the use of lithium in youth suffering from bipolarity.
  
  
  METHODS
  Under the auspices of the Best Pharmaceuticals for Children Act (BPCA), a Written Request (WR) pertaining to the study of lithium in pediatric mania was issued by the United States Food and Drug Administration (FDA) to the National Institute of Child Health and Human Development (NICHD) in 2004. Accordingly, the NICHD issued a Request for Proposals (RFP) soliciting submissions to pursue this research. Subsequently, the NICHD awarded a contract to a group of investigators in order to conduct these studies.
  
  
  RESULTS
  The Collaborative Lithium Trials (CoLT) investigators, the BPCA-Coordinating Center, and the NICHD developed protocols to provide data that will: (1) establish evidence-based dosing strategies for lithium; (2) characterize the pharmacokinetics and biodisposition of lithium; (3) examine the acute efficacy of lithium in pediatric bipolarity; (4) investigate the long-term effectiveness of lithium treatment; and (5) characterize the short- and long-term safety of lithium. By undertaking two multi-phase trials rather than multiple single-phase studies (as was described in the WR), the feasibility of the research to be undertaken was enhanced while ensuring all the data outlined in the WR would be obtained. The first study consists of: (1) an 8-week open-label, randomized, escalating dose Pharmacokinetic Phase; (2) a 16-week Long-Term Effectiveness Phase; (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. The second study consists of: (1) an 8-week, double-blind, parallel-group, placebo-controlled Efficacy Phase; (2) an open-label Long-Term Effectiveness lasting either 16 or 24 weeks (depending upon blinded treatment assignment during the Efficacy Phase); (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. In December of 2006, enrollment into the first of these studies began across seven sites.
  
  
  CONCLUSIONS
  These innovative studies will not only provide data to inform the labeling of lithium in children and adolescents with bipolar disorder, but will also enhance clinical decision-making regarding the use of lithium treatment in pediatric bipolar illness.
  
  
  BACKGROUND
  NCT00442039.
authors.affiliation: Department of Psychiatry, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, OH, USA. robert.findling@uhhospitals.org
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.forename: Jean A
authors.initials: JA
authors.lastname: Frazier
authors.forename: Vivian
authors.initials: V
authors.lastname: Kafantaris
authors.forename: Robert
authors.initials: R
authors.lastname: Kowatch
authors.forename: Jon
authors.initials: J
authors.lastname: McClellan
authors.forename: Mani
authors.initials: M
authors.lastname: Pavuluri
authors.forename: Linmarie
authors.initials: L
authors.lastname: Sikich
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hlastala
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Hooper
authors.forename: Christine A
authors.initials: CA
authors.lastname: Demeter
authors.forename: Denise
authors.initials: D
authors.lastname: Bedoya
authors.forename: Bernard
authors.initials: B
authors.lastname: Brownstein
authors.forename: Perdita
authors.initials: P
authors.lastname: Taylor-Zapata