Efficacy of Quetiapine XR Versus Placebo as Concomitant Treatment to Mood Stabilizers in the Control of Subsyndromal Symptoms of Bipolar Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celso Arango Lopez, Centro de Investigación Biomédica en Red de Salud Mental
ClinicalTrials.gov Identifier:
NCT01197846
First received: September 2, 2010
Last updated: September 18, 2012
Last verified: September 2012
  Purpose

Pilot multicentric, prospective, placebo controlled, randomized double blinded, study of 12 weeks follow-up Adult patients diagnosed of bipolar disorder I or II, in previous treatment with no more than two concomitant mood stabilizers at stable doses and current subsyndromal symptoms, defined as YMRS ≤14 and/ or MADRS≥8 and ≤14 would be included Sub-acute phases would be excluded (at least 8 weeks from last exacerbation would be required for inclusion).


Condition Intervention Phase
Bipolar Disorder
Drug: Quetiapine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Quetiapine XR vs. Placebo as Concomitant Treatment to Mood Stabilizers in the Control of Subsyndromal Symptoms of Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by Centro de Investigación Biomédica en Red de Salud Mental:

Primary Outcome Measures:
  • To assess the efficacy of quetiapine extended release (QTP XR) vs. placebo in the control of bipolar subsyndromal symptoms when added to previous mood stabilizer treatment (lithium/ valproate/lamotrigine) [ Time Frame: Study of 12 weeks follow-up ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the efficacy of QTP XR vs. placebo when added to previous mood stabilizer treatment (lithium/ valproate/lamotrigine) in functional level of bipolar patients with subsyndromal symptoms [ Time Frame: Study of 12 weeks follow-up ] [ Designated as safety issue: Yes ]

Enrollment: 28
Study Start Date: September 2010
Study Completion Date: July 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Quetiapine
Quetiapine 300 mg or 600 mg
Drug: Quetiapine
quetiapine 300 mg or 600 mg
Other Name: Quetiapine XR
Placebo Comparator: Placebo Drug: Placebo
Placebo
Other Name: Placebo

Detailed Description:

Remission of acute episodes usually doesn't correlate with symptomatic or functional recovery in occupational and social domains after (McQueen et al, 2001; Tohen et al, 2000) Ongoing depressive symptoms are the strongest predictor of functional deficits in persons with bipolar disorder (Bauer et al, 2001; Judd et al, 2005). Depressive subsyndromal symptoms are associated to functional impairment in bipolar disorder (Vojta et al, 2001; Altshuler et al, 2002; Yatham et al, 2004) The addition of olanzapine to valproate or lithium provided superior efficacy to valproate or lithium plus placebo in non completely remitted manic and mixed bipolar episodes, mainly through a control of depressive symptoms (Tohen et al, 2002) Quetiapine has demonstrated to be efficacious in the control of depressive symptoms in Bipolar Disorder (BOLDER, EMBOLDEN studies) and in the prevention of recurrences, maintaining the patient in YMRS and MADRS scores under the cut-off point between asymptomatic and subsyndromal states (Studies 126, 127 and 144) Thus it's expectable that adding quetiapine to previous mood stabilizers in bipolar patients with subsyndromal symptoms probably would improve their symptoms, mainly depressive, to levels not only of syndromic but of symptomatic remission, driving to a better functional status Quetiapine extended release would be used because its advantages on quetiapine immediate release regarding an easier and comfortable posology and potential better adherence

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed Consent signature
  2. At least 18 years old
  3. Diagnoses of bipolar disorder I or II (as DSM-IV-TR 4ª Ed codes)
  4. Previous treatment with a mood stabilizer (lithium, valproate or lamotrigine) at stable and optimum doses for at least six weeks prior to the start of the trial (i.e., on the same dose and serum levels within the therapeutic ranges: 0.6-1.2 mEq/l of lithium or 50-100 ug/ml of valproate)
  5. Presenting subsyndromal symptoms at enrolment and randomization point, defined as YMRS ≤ 14 and/ or MADRS ≥ 8 and ≤14
  6. At least one manic, mixed, or depressed episode in the last 5 years
  7. Being able to understand and meet the study requirements

Exclusion Criteria:

  1. Pregnant or nursing women
  2. Mental retardation.
  3. Current active diagnoses of any axis I or II DSM-IV-TR diagnoses different from bipolar disorder I or II. This doesn't apply to nicotine nor caffeine abuse-dependence. Punctual alcohol and/or substances use not constitutive of a diagnoses of abuse or dependence following DSM-IV-TR criteria wouldn't suppose the exclusion of the patient from the study. Anxiety in levels not constitutive of any anxiety disorder within those codified in DSM-IV-TR wouldn't either suppose the exclusion of the patient from the study
  4. Having suffered any acute episode (depressive, manic, or mixed) within the 8 weeks prior to enrolment, as defined in DSM-IV-TR
  5. Patients that, in the investigator's opinion, are at a high risk of suicide or mean a risk of aggression to others.
  6. Having been treated with any antidepressant at randomization.
  7. Having been treated with any mood stabilizer other than lithium/valproate/lamotrigine at randomization.
  8. Having been treated with any oral antipsychotic drug at randomization. Administration of a depot antipsychotic medication within one dosing interval prior to randomization (e.g. Long acting Risperidone 2 weeks; Zuclopenthixol 4 weeks; Pipotiazine 4 weeks; Flufenazine 6 weeks)
  9. Having been treated with any of the following P450-3A4 cytochrome inhibitors in the 14 days prior to inclusion, including: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, fluvoxamine, indinavir, nelfinavir, ritonavir and saquinavir.
  10. Having been treated with any of the following P450-3A4 cytochrome inducers in the 14 days prior to inclusion, including: phenytoin, carbamazepine, barbiturates, rifampicin, St. John's wart, and glucocorticoids.
  11. Any contraindication to the use of quetiapine fumarate in the investigator's opinion (including lack of response to it in previous treatment attempts)
  12. Suffering any medical condition that can effect the absorption, distribution, metabolism or excretion of the study treatment(s).
  13. Suffering any medical condition in decompensation or not receiving inappropriate treatment for it in the investigator's opinion (e.g., hyperthyroidism, angina pectoris, hypertension...)
  14. Suffering unstable diabetes at enrolment or randomization
  15. Absolute neutrophil count ≤ 1.5 x 109 per litre at randomization
  16. Non-compliance with the study plan.
  17. Participation in another clinical trial in the four weeks prior to randomization
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01197846

Locations
Spain
Hospital Clinic I Provincial
Barcelona, Spain, 08036
Hosptial Benito Menni
Barcelona, Spain, 08830
Hospital Universitari de Bellvitge
Barcelona, Spain, 08907
Hospital Santa Creu I Sant Pau
Barcelona, Spain, 08025
Parc Sanitari Sant Joan de Deu
Barcelona, Spain, 08940
Hospital General Universitario Gregorio Marañon
Madrid, Spain, 28009
Hospital Universitario Ramon Y Cajal
Madrid, Spain, 28034
Centro de Salud Menta II
Oviedo, Spain, 33011
Hosptial Clinico Valencia/ CSM Foios
Valencia, Spain, 46134
Hospital Santiago Apostol
Vitoria, Spain, 01004
Sponsors and Collaborators
Centro de Investigación Biomédica en Red de Salud Mental
Investigators
Principal Investigator: Eduard Vieta, PhD Hospital Clinic I Provincial. Barcelona. Spain
Principal Investigator: Ana Gonzalez Pinto Hospital Santiago Apostol. Vitoria. Spain
Principal Investigator: Benedikt Amann Hospital Benito Menni. Barcelona. Spain
Principal Investigator: Celso Arango Hospital General Universitario Gregorio Marañon. Madrid. Spain
Principal Investigator: Jose Manuel Crespo Hospital Universitari de Bellvitge. Barcelona. Spain
Principal Investigator: Julio Bobes Centro de Salud Mental II. Oviedo. Spain
Principal Investigator: Josefina Perez Hospital Santa Creu I Sant Pau. Barcelona. Spain
Principal Investigator: Gabriel Selva Hospital Clinico de Valencia/ CSM Foios. Valencia. Spain
Principal Investigator: Belen Arranz Parc Sanitari Sant Joan de Deu. Barcelona. Spain
Principal Investigator: Jeronimo Saiz Hospital Universitario Ramon y Cajal. Madrid. Spain
  More Information

No publications provided

Responsible Party: Celso Arango Lopez, MD; PhD, Centro de Investigación Biomédica en Red de Salud Mental
ClinicalTrials.gov Identifier: NCT01197846     History of Changes
Other Study ID Numbers: D1443L00079
Study First Received: September 2, 2010
Last Updated: September 18, 2012
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica

Additional relevant MeSH terms:
Bipolar Disorder
Disease
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Pathologic Processes
Quetiapine
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on September 22, 2014