Safety and Efficacy Study of Lithium for the Treatment of Pediatric Mania.
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Study Design This is the second study of a multiphase, multicenter trial that will
      comprehensively examine lithium in the treatment of pediatric participants with bipolar I
      disorder. In order to examine the treatment of bipolar disorder with lithium, this study will
      include four phases of treatment. The first phase, the Efficacy Phase, will include
      participants being randomized to either lithium or placebo for 8 weeks to determine the
      efficacy of lithium in the treatment of children and adolescents with bipolar I disorder.
      Once participants complete the Efficacy Phase, participants may be eligible to continue in
      the Long- Term Effectiveness Phase for a maximum of 24 weeks of lithium treatment.
      Subsequently, participants meeting response criteria during the Long-Term Effectiveness Phase
      will be eligible to continue in the Discontinuation Phase. During the Discontinuation Phase,
      participants will be randomized to either placebo or lithium treatment for up to 28 weeks.
      Finally, those participants who experience a mood relapse during the Discontinuation Phase
      will be enrolled in an Open Label Restabilization Phase and treated with lithium for up to 8
      weeks.
    

Detailed description: 
      The following are the objectives of this study:

        1. To determine if lithium is more efficacious in reducing symptoms of mania than placebo.

        2. To describe the short-term safety of lithium in the pediatric population relative to
           placebo treatment.

        3. To examine the effectiveness and efficacy of lithium as a maintenance treatment for
           children and adolescents with bipolar I disorder.

        4. To examine the long-term and short-term safety and tolerability of lithium in pediatric
           bipolar I disorder.

        5. To examine the effects of lithium treatment over time on specific aspects of cognitive
           functioning that have been reported to be adversely affected by lithium in the adult
           population.

        6. More specifically, to determine the integrity of fine-motor, attention, verbal memory,
           and selected executive function domains prior to treatment at baseline, at the end of
           week 8/early termination of the Efficacy Phase, and at the end of week 24/early
           termination from the Long- Term Effectiveness Phase (after 24/32 weeks of lithium
           treatment).

        7. To examine the relationship between systemic exposure to lithium and effectiveness and
           toxicity.

        8. To examine the long-term safety and tolerability of combination therapy, lithium plus
           other psychotropic agents, in pediatric bipolar I disorder.

        9. To critically assess the efficacy of lithium for prophylaxis against recurrence of mood
           symptoms in children and adolescents.

       10. In those participants who discontinue treatment with lithium and experience a mood
           relapse, to determine the duration of lithium treatment necessary before
           re-stabilization is achieved.

       11. To evaluate the influence of intrinsic factors [e.g. age, gender, race, renal function,
           height, (measured by stadiometer) and weight] on lithium exposure.

      The Study population for this study: Children and adolescents 7- 17 years of age who meet
      DSM-IV diagnostic criteria for Bipolar I (mania, mixed mania) without psychotic symptoms as
      determined by a child and adolescent psychiatrist will be eligible for this study.
    

Intervention name(s): Lithium Carbonate; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Participants weighing ≥ 30 kg who are randomized to receive active lithium will begin treatment at 300 mg TID at visit 1 (total dose 900 mg). Participants weighing < 30 kg who are randomized to receive active lithium will begin treatment at 300 mg BID the day after visit 1 (total dose 600 mg). Based on the participant's response and tolerability, the dose will be increased by 300mg three days after the baseline visit and at scheduled in-office visits to the maximum tolerated dose. One mid-week dose increase will be scheduled in addition to the weekly increases at the scheduled in-clinic visits. On day 3 (+/- 2 days), a dose increase of 300 mg may occur based on the results of a telephone call placed by the study investigator to the participant's parent/guardian. During the telephone call, the prescribing clinician will assess medication adherence, adverse events, and overall improvement since baseline.; Participants who are randomized to receive placebo during the Efficacy Phase will receive matching placebo capsules. Dosing will be titrated as described for active lithium.
Other intervention name(s): Lithium capsules; Placebo capsules
Intervention MeSH terms: Lithium Carbonate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment