Research

The Collaborative Lithium Trials (CoLT): specific aims, methods, and implementation

Robert L Findling¹ , Jean A Frazier² , Vivian Kafantaris³ , Robert Kowatch⁴ , Jon McClellan⁵ , Mani Pavuluri⁶ , Linmarie Sikich⁷ , Stefanie Hlastala⁵ , Stephen R Hooper^7,8 , Christine A Demeter¹ , Denise Bedoya¹ , Bernard Brownstein⁹ and Perdita Taylor-Zapata¹⁰

¹Department of Psychiatry, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, OH, USA

²Cambridge Health Alliance and Department of Psychiatry, Harvard Medical School, Cambridge, MA , USA

³The Feinstein Institute for Medical Research of the North Shore—Long Island Health System, Manhasset, NY, USA

⁴Division of Psychiatry, Cincinnati Children’s Hospital, Cincinnati, OH, USA

⁵Department of Psychiatry, University of Washington, Seattle, WA, USA

⁶Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA

⁷Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

⁸Clinical Center for the Study of Development and Learning of the Carolina Institute of Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

⁹Best Pharmaceuticals for Children Act-Coordinating Center, Premier Research, Philadelphia, PA, USA

¹⁰Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA

author email corresponding author email

Child and Adolescent Psychiatry and Mental Health 2008, 2:21doi:10.1186/1753-2000-2-21

Published:	12 August 2008

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.

Conclusion

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.

Trial Registration

NCT00442039