Lithium for the Treatment of Pediatric Mania

NCT00442039 | Completed Phase 2 DMC

• 2 other identifiers: NICHD-2005-07-01DUNS No. 07-775-8407
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bipolar I Disorder Without Psychotic Symptoms

Keywords

Mania, Lithium, Bipolar, BPCA, pediatrics

Outcome Measures

Primary Outcomes (5)

• Mean Change in YMRS summary score by treatment

  Measure of efficacy

  8 weeks

• Mean change in YMRS parent score

  Measure of efficacy

  8 weeks

• Mean change in YMRS child score

  Measure of efficacy

  8 weeks

• Rate of treatment emergent adverse events

  During administration of study drug

• Dosing - PK

  8 weeks

Study Arms (4)

Lithium dosing 1

EXPERIMENTAL

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.

Drug: Lithium Carbonate

Lithium dosing 2

EXPERIMENTAL

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

Lithium dosing 3

EXPERIMENTAL

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: Lithium Carbonate

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Lithium Carbonate DRUG

The starting dose of lithium was 300 mg for patients weighing \< 20 kg

Lithium dosing 1

Placebo DRUG

During the third phase, which is the Discontinuation Phase, patients will be randomized to either placebo or lithium treatment for up to 28 weeks.

Placebo

Eligibility Criteria

• Age: 7 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The patient was between the ages of 7 years and 17 years, 11 months at time of first dose.
• 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.
• The patient had a score of ≥ 20 on the YMRS at screening and baseline.
• 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.
• Patients with comorbid conditions (attention deficit hyperactivity disorder \[ADHD\], conduct disorder) were eligible to participate.
• 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.
• 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.
• 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.
• The patient"s ECG and blood work (including complete blood count \[CBC\], electrolytes, etc.) showed no clinically significant abnormalities.

You may not qualify if:

• The patient was clinically stable on current medication regiment for bipolar disorder.
• 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.
• The patient had a current DSM-IV diagnosis of Substance Dependence.
• The patient had a positive drug screen at screening and on retest 1-3 weeks later.
• The patient had symptoms of mania that may have been attributable to a general medical condition, or secondary to use of medications (eg, corticosteroids)
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• The patient had current psychotherapy treatments provided outside the study initiated within 4 weeks prior to screening.
• The patient had a previous adequate trial with lithium (at least 4 weeks with lithium serum levels between 0.8-1.2 mEq/L).
• The patient had a history of allergy to lithium.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

CASE Western Reserve University

Cleveland, Ohio, 44126, United States

Location

Related Publications (2)

• Findling RL, McNamara NK, Pavuluri M, Frazier JA, Rynn M, Scheffer R, Kafantaris V, Robb A, DelBello M, Kowatch RA, Rowles BM, Lingler J, Zhao J, Clemons T, Martz K, Anand R, Taylor-Zapata P. Lithium for the Maintenance Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Discontinuation Study. J Am Acad Child Adolesc Psychiatry. 2019 Feb;58(2):287-296.e4. doi: 10.1016/j.jaac.2018.07.901. Epub 2018 Nov 26.

  PMID: 30738555 DERIVED

• Findling RL, Frazier JA, Kafantaris V, Kowatch R, McClellan J, Pavuluri M, Sikich L, Hlastala S, Hooper SR, Demeter CA, Bedoya D, Brownstein B, Taylor-Zapata P. The Collaborative Lithium Trials (CoLT): specific aims, methods, and implementation. Child Adolesc Psychiatry Ment Health. 2008 Aug 12;2(1):21. doi: 10.1186/1753-2000-2-21.

  PMID: 18700004 DERIVED

MeSH Terms

Conditions

Mania

Interventions

Lithium Carbonate

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Officials

• Robert L Findling, MD

  Case Western University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2007
• First Posted: March 1, 2007
• Study Start: December 1, 2006
• Primary Completion: April 1, 2009
• Study Completion: September 1, 2009
• Last Updated: February 28, 2012

Record last verified: 2012-02

Locations

US (1)