Lithium for the Treatment of Pediatric Mania

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00442039
First received: February 27, 2007
Last updated: February 24, 2012
Last verified: February 2012

February 27, 2007
February 24, 2012
December 2006
April 2009   (final data collection date for primary outcome measure)
  • Mean Change in YMRS summary score by treatment [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measure of efficacy
  • Mean change in YMRS parent score [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measure of efficacy
  • Mean change in YMRS child score [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measure of efficacy
  • Rate of treatment emergent adverse events [ Time Frame: During administration of study drug ] [ Designated as safety issue: Yes ]
  • Dosing - PK [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • To examine the effectiveness and efficacy of lithium as a maintenance treatment for children and adolescents with bipolar I disorder
  • To describe evidence-based dosing strategies for lithium in children and adolescents
  • To examine the long-term and short-term safety and tolerability of lithium in pediatric bipolar disorder
  • To characterize the pharmacokinetics/biodisposition of lithium in pediatric patients
Complete list of historical versions of study NCT00442039 on ClinicalTrials.gov Archive Site
Not Provided
  • To describe and compare the pharmacokinetic profile and systemic exposure of lithium after single and multiple doses in children and adolescents
  • To evaluate the influence of intrinsic factors (e.g. age, gender, race, renal function, height (measured by stadiometer) and weight) on lithium exposure
  • To describe lithium exposure in the pediatric population to what is known in adults
  • To examine the relationship between the systemic exposure and effectiveness and toxicity
  • To examine the long-term safety and tolerability of combination therapy, lithium plus other psychotropic agents, in pediatric bipolar disorder
  • To critically assess the efficacy of lithium for prophylaxis against recurrence of mood episodes in children and adolescents
  • In those patients who discontinue treatment with lithium and experience a mood relapse, to determine the duration of lithium treatment necessary before re-stabilization is achieved
Not Provided
Not Provided
 
Lithium for the Treatment of Pediatric Mania
Pediatric Pharmacokinetic and Tolerability Study of Lithium for the Treatment of Pediatric Mania Followed by an Open Label Long Term Safety Period, Discontinuation Phase, and Restabilization Period.

This clinical trial is being performed under the Best Pharmaceuticals for Children Act, signed into law in 2002 in order to improve pediatric labeling for off-patent drugs. The purpose of this study is to examine the efficacy and safety of lithium in the treatment of pediatric patients with bipolar I disorder.

This is a multiphase, multicenter, trial that will comprehensively examine lithium in the treatment of pediatric patients 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 Pharmacokinetic Phase, will include 8 weeks of Open Label treatment to determine empirically based dosing strategies for children and adolescents with bipolar disorder. Patients completing the Pharmacokinetic Phase, may be eligible to continue in the Long-Term Effectiveness Phase for a maximum of 16 weeks of lithium treatment. Subsequently, patients meeting response criteria during the Long-Term Effectiveness Phase will be eligible to continue in the Discontinuation Phase. During the Discontinuation Phase, patients will be randomized to either placebo or lithium treatment for up to 28 weeks. Finally, those subjects 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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Bipolar I Disorder Without Psychotic Symptoms
  • Drug: Lithium Carbonate
    The starting dose of lithium was 300 mg for patients weighing < 20 kg
  • Drug: Lithium Carbonate
    The dose of lithium was increased weekly by 300 mg to maximum tolerated dose depending upon the patient‟s response and tolerability. The starting dose of lithium was 900 mg and the dose of lithium was increased weekly by 300 mg to maximum tolerated dose depending upon the patient‟s response and tolerability
  • Drug: Lithium Carbonate
    The starting dose of lithium was 900 mg and the lithium dose was increased by 300 mg every 3 days, (no more than twice weekly) to maximum tolerated dose based upon the patient‟s response and tolerability.
  • Drug: Placebo
    During the third phase, which is the Discontinuation Phase, patients will be randomized to either placebo or lithium treatment for up to 28 weeks.
  • Experimental: Lithium dosing 1
    The starting dose of lithium was 300 mg for patients weighing < 20 kg [no patients were enrolled that weighed less than 20 kg] and 600 mg for patients weighing ≥ 20 kg.
    Intervention: Drug: Lithium Carbonate
  • Experimental: Lithium dosing 2
    The starting dose of lithium was 900 mg and the dose of lithium was increased weekly by 300 mg to maximum tolerated dose depending upon the patient‟s response and tolerability.
    Intervention: Drug: Lithium Carbonate
  • Experimental: Lithium dosing 3
    The starting dose of lithium was 900 mg and the lithium dose was increased by 300 mg every 3 days, (no more than twice weekly) to maximum tolerated dose based upon the patient‟s response and tolerability.
    Intervention: Drug: Lithium Carbonate
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
61
September 2009
April 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. The patient was between the ages of 7 years and 17 years, 11 months at time of first dose.
  2. The patient met DSM-IV diagnostic criteria, as assessed by a semi-structured assessment (Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime [KSADS-PL]) and a separate clinical interview with a child/adolescent psychiatrist for manic or mixed episodes in Bipolar I disorder.
  3. The patient had a score of ≥ 20 on the YMRS at screening and baseline.
  4. The patient and legal guardian understood the nature of the study and were able to comply with protocol requirements. The legal guardian gave written informed consent and the youth, written assent.
  5. Patients with comorbid conditions (attention deficit hyperactivity disorder [ADHD], conduct disorder) were eligible to participate.
  6. If female: the patient was premenarchal, or was incapable of pregnancy because of a hysterectomy, tubal ligation, or spousal/partner sterility. If sexually active and capable of pregnancy, the patient must have been using an acceptable method of contraception (hormonal contraceptives, intrauterine device, spermicide and barrier) for at least 1 month prior to study entry and agreed to continue to use one of them for the duration of the study. If sexually abstinent and capable of pregnancy, the patient agreed to continue abstinence or to use of an acceptable method of birth control (either intrauterine device or spermicide and barrier) should sexual activity commence.
  7. If female, the patient had a negative quantitative serum ß-human chorionic gonadotrophin hormone pregnancy test at screening and a negative qualitative urine pregnancy test at baseline, if female.
  8. Patients with a history of substance abuse were eligible to participate if they agreed to continue to abstain from drugs during the trial and had a negative drug screen at screening or prior to baseline.
  9. The patient was willing and clinically able to washout (approximately 5 half-lives) of exclusion medications during the screening period and prior to the administration of lithium. (No stable patients were asked to discontinue medications.)
  10. The patient‟s ECG and blood work (including complete blood count [CBC], electrolytes, etc.) showed no clinically significant abnormalities.

Exclusion Criteria:

  1. The patient was clinically stable on current medication regiment for bipolar disorder.
  2. The patient had a current or lifetime diagnosis of Schizophrenia or Schizoaffective Disorder, a Pervasive Developmental Disorder (Austin Screening Questionnaire score > 15), Anorexia Nervosa, Bulimia Nervosa, or Obsessive-Compulsive Disorder.
  3. The patient had a current DSM-IV diagnosis of Substance Dependence.
  4. The patient had a positive drug screen at screening and on retest 1-3 weeks later.
  5. The patient had symptoms of mania that may have been attributable to a general medical condition, or secondary to use of medications (eg, corticosteroids)
  6. The patient had evidence of any serious and/or unstable neurological illness for which treatment under the auspices of this study would have been contra-indicated.
  7. The patient had any serious, unstable medical illness or clinically significant abnormal laboratory assessments that would adversely impact the scientific interpretability or unduly increase the risks of the protocol.
  8. The patient had a current general medical condition including neurological disease, diabetes mellitus, thyroid dysfunction, or renal dysfunction that might have been affected adversely by lithium, could have influenced the efficacy or safety of lithium, or would have complicated interpretation of study results.
  9. The patient had evidence of current serious homicidal/suicidal ideation such that in the treating physician's opinion it was appropriately safe for the patient to participate in this study.
  10. The patient had evidence of current active hallucinations and delusions such that in the treating physician's opinion it was not appropriately safe for the patient to participate in this study.
  11. The patient had concomitant prescription of over-the-counter medication or nutritional supplements that would interact with lithium or the patient‟s physical or mental status.
  12. The patient had any use of psychotropic agents other than stimulants within the preceding 2 weeks, including antipsychotics, monoamine oxidase inhibitors, antidepressants; use of stimulants within the preceding week; or fluoxetine or depot antipsychotics within the past month.
  13. The patient had current psychotherapy treatments provided outside the study initiated within 4 weeks prior to screening.
  14. The patient had a previous adequate trial with lithium (at least 4 weeks with lithium serum levels between 0.8-1.2 mEq/L).
  15. The patient had a history of allergy to lithium.
  16. The patient had psychiatric hospitalization within 1 month of screening for psychosis or serious homicidal/serious suicidal ideation.
  17. Clinician‟s judgment was that the patient was not likely to be able to complete the study as an outpatient due to psychiatric reasons.
  18. The patient had a history of lithium intolerance.
  19. Females who were currently pregnant or lactating.
  20. Sexually active females who, in the investigators‟ opinion, were not using an adequate form of birth control.
  21. Patients who were unable to swallow the study medication.
  22. Patients for whom a baseline YMRS score of < 20 was anticipated.
  23. Patients with an IQ < 70 (determined using the Wechsler Abbreviated Scales of Intelligence [WASI] Vocabulary and Matrix Reasons Subscales).
Both
7 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00442039
NICHD-2005-07-01, DUNS No. 07-775-8407
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not Provided
Principal Investigator: Robert L Findling, MD Case Western University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP