Safety and Efficacy Study of Lithium for the Treatment of Pediatric Mania.

NCT01166425 | Completed Phase 2 DMC

• 1 other identifier: NICHD-2005-07-2
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Bipolar Disorder

Outcome Measures

Primary Outcomes (1)

• YMRS score

  Significant changes in YMRS scores from baseline to the end of each study phase. YMRS scores are questionnaires to assess pediatric mania.

  >17 months

Secondary Outcomes (2)

• Clinical Global Impressions Scale- Severity and Improvement

  >17 months

• Children Depression Rating Scale-Revised

  >17 months

Study Arms (2)

Lithium Carbonate

ACTIVE COMPARATOR

Participants weighing ≥ 30 kg who are randomized to receive active lithium will begin treatment at 300 mg TID (three times a day) 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 (two times a day) 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.

Drug: Lithium Carbonate

placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Lithium Carbonate DRUG

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.

Also known as: Lithium capsules

Lithium Carbonate

Placebo DRUG

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.

Also known as: Placebo capsules

placebo

Eligibility Criteria

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

You may qualify if:

• Participants aged 7 years to 17 years, 11 months old at time of first dose
• Participants must meet DSM-IV diagnostic criteria, as assessed by a semi-structured assessment (KSADS-PL) and a separate clinical interview with a child/adolescent psychiatrist for manic or mixed episodes in bipolar I disorder
• Score of \> 20 on the YMRS at screening and baseline
• The participant and legal guardian must understand the nature of the study and be able to comply with protocol requirements. The legal guardian must give written informed consent and the youth, written assent
• If female: is premenarchal, or is incapable of pregnancy because of a hysterectomy, tubal ligation, or spousal/partner sterility. If sexually active and capable of pregnancy, has been using an acceptable method of contraception (hormonal contraceptives, intrauterine device, spermicide and barrier) for at least one month prior to study entry and agrees to continue to use one of these for the duration of the study. If sexually abstinent and capable of pregnancy, agrees to continued abstinence or to use of an acceptable method of birth control should sexual activity commence
• Has a negative quantitative serum ß-human chorionic gonadotrophin hormone pregnancy test at screening and a negative qualitative urine pregnancy test at baseline, if female
• Participants with a history of substance abuse may participate if they agree to continue to abstain from drugs during the trial and have a negative drug screen at screening or prior to baseline. Those with an initial positive drug screen during screening may have another screen done 1-3 weeks later while in screening, and a negative result will allow the participant to participate
• ECG and bloodwork including CBC, electrolytes, etc. (as per Safety assessment procedures listed in Table 6) showing no clinically significant abnormalities

You may not qualify if:

• Participant who is clinically stable on current medication regimen for bipolar disorder
• A current or lifetime diagnosis of Schizophrenia or Schizoaffective Disorder, a Pervasive Developmental Disorder (ASQ score \> 15), Anorexia Nervosa, Bulimia Nervosa, or Obsessive-Compulsive Disorder
• Current DSM-IV diagnosis of Substance Dependence
• Positive drug screen at screening and on retest 1-3 weeks later
• Participants with symptoms of mania that may be attributable to a general medical condition, or secondary to use of medications (e.g., corticosteroids)
• Evidence of any serious, unstable neurological illness for which treatment under the auspices of this study would be contraindicated
• 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
• Current general medical condition including neurological disease, diabetes mellitus, thyroid dysfunction, or renal dysfunction that might be affected adversely by lithium, could influence the efficacy or safety of lithium, or would complicate interpretation of study results
• Evidence of current serious homicidal/suicidal ideation such that in the treating physician's opinion it would not be appropriately safe for the participant to participate in this study
• Evidence of current active hallucinations and delusions such that in the treating physician's opinion it would not be appropriately safe for the participant to participate in this study
• Concomitant prescription of over-the-counter medication or nutritional supplements (e.g., ibuprofen, naproxen, St John's wort) that would interact with lithium or affect the participant's physical or mental status
• Concomitant psychotherapy treatments provided outside the study initiated within 4 weeks prior to screening
• Previous adequate trial with Li+ (at least 4 weeks with Li+ serum levels between 0.8-1.2 mEq/L)
• History of allergy to lithium or lithium intolerance
• Psychiatric hospitalization within 1 month of screening for psychosis or serious homicidal/serious suicidal ideation

Sponsors & Collaborators

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

Study Sites (11)

Childrens National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

University of Illinois at Chicago

South Chicago Heights, Illinois, 60612, United States

Location

University of Kansas School of Medicine

Psychiatry and Behavioral Sciences, 1010 N Kansas St, Wichita, Kansas, 67214, United States

Location

University of Massachusetts Medical School

Biotech One Suite 100, 365 Plantation, Worcester, Massachusetts, 01605, United States

Location

The Zucker Hillside Hospital

Glen Oaks, New York, 11004, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of North Carolina - Chapel Hill

Department of Psychiatry, CB 7160, Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 10032, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Seattle Childrens Hospital Research Institute

Seattle, Washington, 98101, 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, Robb A, McNamara NK, Pavuluri MN, Kafantaris V, Scheffer R, Frazier JA, Rynn M, DelBello M, Kowatch RA, Rowles BM, Lingler J, Martz K, Anand R, Clemons TE, Taylor-Zapata P. Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Study. Pediatrics. 2015 Nov;136(5):885-94. doi: 10.1542/peds.2015-0743. Epub 2015 Oct 12.

  PMID: 26459650 DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Lithium Carbonate; Lithium

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Metals, Alkali; Elements; Metals, Light; Metals

Study Officials

• Robert Findling, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2010
• First Posted: July 21, 2010
• Study Start: June 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: October 9, 2013

Record last verified: 2013-05

Locations

US (11)