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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00202293




Registration number
NCT00202293
Ethics application status
Date submitted
14/09/2005
Date registered
20/09/2005
Date last updated
31/08/2018

Titles & IDs
Public title
Comparison of Combination Olanzapine+Lithium or Chlorpromazine+Lithium in Treatment of First Manic Episode With Psychotic Features
Scientific title
Comparison of Combination Olanzapine and Lithium and Combination Chlorpromazine and Lithium in the Treatment of a First Manic Episode With Psychotic Features.
Secondary ID [1] 0 0
2001.013
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bipolar Disorder 0 0
Schizoaffective Disorder 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Other mental health disorders
Mental Health 0 0 0 0
Depression
Mental Health 0 0 0 0
Psychosis and personality disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Lithium and olanzapine -

Active comparator: Lithium and chlorpormazine -

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Intensity of side effects
Timepoint [1] 0 0
8 weeks
Primary outcome [2] 0 0
¨The frequency of treatment-emergent adverse events (events that first appear or worsen during the study period) will be compared between both groups.
Timepoint [2] 0 0
8 weeks
Primary outcome [3] 0 0
¨The frequency of side effects as rated with the UKU scale will be compared between both groups.
Timepoint [3] 0 0
8 weeks
Primary outcome [4] 0 0
¨Weight gain will be compared between both groups.
Timepoint [4] 0 0
8 weeks
Primary outcome [5] 0 0
¨Frequency of changes in vital signs and laboratory findings will be compared between both groups.
Timepoint [5] 0 0
8 weeks
Primary outcome [6] 0 0
Subjective well being
Timepoint [6] 0 0
8 weeks
Primary outcome [7] 0 0
¨Total scores on the DAI and the SWN will be compared between both groups.
Timepoint [7] 0 0
8 weeks
Secondary outcome [1] 0 0
Adherence
Timepoint [1] 0 0
8 weeks
Secondary outcome [2] 0 0
¨Degree of adherence to the treatment as scored on the MARS will be compared between both groups.
Timepoint [2] 0 0
8 weeks
Secondary outcome [3] 0 0
Response to treatment
Timepoint [3] 0 0
8 weeks
Secondary outcome [4] 0 0
¨End point analysis: Mean change in various scales from baseline to week 4 and week 8 will be used to compare the efficacy of the two treatments:
Timepoint [4] 0 0
8 weeks
Secondary outcome [5] 0 0
¨Primary efficacy analysis will be assessed by comparing the mean change in theYMRS total score.
Timepoint [5] 0 0
8 weeks
Secondary outcome [6] 0 0
¨Secondary efficacy analysis will be assessed by comparing the mean change in CGI-BP total score and in BPRS total score.
Timepoint [6] 0 0
8 weeks
Secondary outcome [7] 0 0
¨Response analysis: Response is defined as at least a 50% drop in the total YMRS total score from base line to the 8-weeks end point. Euthymia is defined as a total score on the YMRS of no greater than 12 at end point. The number of patients reaching bot
Timepoint [7] 0 0
8 weeks
Secondary outcome [8] 0 0
Incidence of depressive episodes
Timepoint [8] 0 0
8 weeks
Secondary outcome [9] 0 0
¨A worsening in the HAMD-21 score of at least 3 points will be used as a definition of a clinically detectable worsening in depressive symptoms.
Timepoint [9] 0 0
8 weeks
Secondary outcome [10] 0 0
Six and 12 months outcome
Timepoint [10] 0 0
12 months
Secondary outcome [11] 0 0
Definition of recovery:
Timepoint [11] 0 0
12 months
Secondary outcome [12] 0 0
¨Syndromic recovery: Eight contiguous weeks [50] during which the patient no longer meets criteria for a manic, mixed, or depressive syndrome. Recovery from each of these syndromes is based on DSM-IV criteria and is operationalised as follows: manic synd
Timepoint [12] 0 0
12 months
Secondary outcome [13] 0 0
¨Symptomatic recovery: Eight contiguous weeks [50] during which the patient experiences minimal to no psychiatric symptoms, operationalized as follows: Young Mania Rating Scale total score of 5 or less, Hamilton depression scale total score of 10 or les
Timepoint [13] 0 0
12 months
Secondary outcome [14] 0 0
¨Relapse: Relapse is defined as the return of symptoms after a remission of less than 8 weeks.
Timepoint [14] 0 0
12 months
Secondary outcome [15] 0 0
¨Recurrence: Recurrence is defined as return of symptoms after recovery.
Timepoint [15] 0 0
12 months
Secondary outcome [16] 0 0
¨Functional recovery: Return to premorbid levels of function for at least 8 contiguous weeks [50]. To assess functional recovery, seven of the nine general items from the Premorbid Adjustment Scale are evaluated at the 6 and 12-month follow-up visit for
Timepoint [16] 0 0
12 months

Eligibility
Key inclusion criteria
* Male and female patients aged 15 to 29.
* Experiencing a first episode psychosis.
* Meet DSM-IV criteria for bipolar either manic or mixed episode, or schizoaffective disorder manic episode.
* Minimum score of 20 on the YMRS
* Written informed consent to participation.
Minimum age
15 Years
Maximum age
29 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients at immediate risk of committing harm to self or others
* Use of neuroleptics or mood-stabilisers in the two months preceding admission to EPPIC
* Organic mental disease, including mental retardation
* History of clinically significant illness (liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological or metabolic disturbances).
* Clinically relevant biochemical or hematological abnormalities.
* Pregnant or lactating woman
* History of epilepsy
* History of severe drug allergy or hypersensitivity
* Non fluency in English.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2001
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2015
Sample size
Target
Accrual to date
Final
83
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
ORYGEN Youth Health - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville

Funding & Sponsors
Primary sponsor type
Other
Name
Melbourne Health
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Aim: In a population of first episode manic patients with psychotic features, we want to compare the side effect profile, the degree of adherence and the subjective well being, as well as the efficacy of two treatments: The standard treatment currently applied (lithium + chlorpromazine) and an alternative treatment more recently introduced (lithium + olanzapine). In addition, we want to study retrospectively the development of bipolar disorder and study prospectively the 6 and 12-month outcome of a cohort of patients presenting a first manic episode with psychotic features.

Research Background: While the efficacy of lithium in the treatment of acute mania has been established by numerous studies, it is also known that up to 50% of the patients fail to respond when it is prescribed alone. It is therefore common practice to complement the treatment, most commonly with antipsychotics and benzodiazepines. It has been suggested that antipsychotic agents are faster acting and are superior in controlling hyperactivity compared to lithium, whereas mood stabilisation is better achieved by lithium, Typical antipsychotics, such as chlorpromazine, may therefore be useful as adjunctive medication to mood stabilisers, especially within the first few weeks of treatment of acute mania, and for patients exhibiting psychotic symptoms or hyperactivity. They however can induce side effects (somnolence, dizziness, dry mouth, extrapyramidal side effects such as rigidity of the muscles, and possibly tardive dyskinesia (involuntary movements or contraction of muscles), as well as akathysia (sense of restlessness). They finally have been suspected to contribute to the occurrence of post-manic depression. Recent publications in chronic populations have shown that atypical antipsychotics, such as olanzapine, are also an effective adjunctive treatment. Olanzapine has the important advantage to induce a very low incidence of extrapyramidal side effects, including tardive dyskinesia. It can however induce somnolence, dizziness, dry mouth, and rather commonly weight gain. Moreover, some authors have reported that olanzapine might induce mania. Both treatments appear then to have positive effects as well as undesirable side effects. Our project is to compare them. The literature concerning first episode mania is sparse, particularly in the domain of pharmacotherapy. One retrospective study showed that 77% of the patients received antipsychotics at discharge and 25% at 6 months follow-up. No comparison has however been made between typical and atypical antipsychotics, and there are no specific treatment guidelines of first episode mania with psychotic features.

Project Summary: The hypothesis is that olanzapine and chlorpromazine will have a comparable efficacy as adjunctive treatment of the acute manic episode with psychotic features. We however think olanzapine will induce less side effects and will be better accepted by the patients, and therefore that the adherence to the treatment will be better than with chlorpromazine. We finally think the subjective sense of well being will be greater with olanzapine than with chlorpromazine.We will recruit 75 patients at the time of their first admission for mania with psychotic features at EPPIC. After signature of the informed consent, we will perform a baseline assessment first to confirm the diagnosis, and second to evaluate the level of psychopathology. The patients will then be randomly selected to receive either a treatment of lithium and olanzapine or a treatment of lithium and chlorpromazine. By the end of the study there will be 37 patients in each group.The patients will go through a baseline assessment including physical examination and usual laboratory investigation to exclude any physical illness. They will also go through a one-hour assessment of psychopathology. Between day 2 and 3 they will go through 2 hours of interview to reassess diagnosis and personal history. They will thereafter be assessed weekly for eight weeks on various dimensions: evolution of the intensity of the symptoms, appearance of depressive symptoms, occurrence of side effects and degree of adherence to the treatment, in an 1-hour interview. Subjective well being and quality of life will re evaluated at week 4 and 8, adding 45 minutes to the duration of the interview. This is a flexible dose, open trial, which means the doctor in charge of the patient will know which medication is being prescribed, and that he will be allowed to adapt the dosage according to what he feels necessary. This research project will allow us to organise a more specialised clinic for the care of first episode manic patients. We will take this opportunity to study carefully the months preceding the appearance of the first episode in order to try to reconstruct the prodrome of bipolar disorders. We will also, in an extension phase of the study, look at the long term outcome (at 6 and 12 months) of a first episode of mania.
Trial website
https://clinicaltrials.gov/study/NCT00202293
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Philippe Conus
Address 0 0
ORYGEN Youth Health & Department of Psychiatry, The University of Lausanne
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00202293