E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with psychotic symptoms, diagnosed with schizophrenia |
|
E.1.1.1 | Medical condition in easily understood language |
Schizophrenia with predominantly
- negative symtoms: loss of interest, social withdrawl, affect flattening
- decline in cognitive functions (i.e. working memory) |
|
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To study whether cognitive functions in patients with schizophrenia are affected by addition of L-dopa to optimized conventional (D2-blocking) antipsychotic treatment 2. To study whether negative psychotic symptoms are affected by addition of L-dopa to optimized conventional (D2-blocking) antipsychotic treatment |
|
E.2.2 | Secondary objectives of the trial |
3. To study whether positive psychotic symptoms will be affected by L-dopa addition to optimized conventional (D2-blocking) antipsychotic treatment? 4. To study whether extrapyramidal symptoms, as frequently seen in patients with schizophrenia who are treated with conventional (D2-blocking) antipsychotic treatment, are reduced by addition of L-dopa. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All patients will be recruited from the Psychiatry ward of the Erasmus Medical Center, Rotterdam, and diagnosed according to DSM-IV criteria by a senior psychiatrist Patients will be included if they meet the criteria for schizophrenia. Further inclusion criteria inpatients aged 18-40 years with a diagnosis of schizophrenia, stable under haloperidol or risperidone treatment (≤20 points, or >3 points on no more than three items on PANSS positive symptom scale), with significant negative symptoms (total of >20 points, or >3 points on two items on PANSS negative symptom scale) are eligible for the study. |
|
E.4 | Principal exclusion criteria |
pregnancy,use of psychotropic medication other than benzodiazepines serious neurological disorders. Subjects will also be excluded when they cannot understand Dutch language sufficiently to understand the purposes and implications of the experiment. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
There will be three primary outcome measures. The first primary outcome measure is the change in verbal memory, as compared between patients receiving placebo vs those receiving L-Dopa. Verbal memory is assessed by the Hopkins Verbal Learning Test-Revised (HVLT-R), which is included in the MATRICS. Earlier studies have reported a great difference in verbal memory function between patients with schizophrenia and healthy controls (e.g. Cascella et al., 2008). We expect L-dopa addition will lead to an improvement of verbal memory function of at least 25% towards the level of healthy control subjects. Based on the effect size found in earlier studies comparing patients with schizophrenia with healthy controls (Cascella et al., 2008), a power analysis indicates we would need to include approximately 40 patients in order to reliably show a 25% increase in verbal memory function. The second primary outcome measure is the alteration in working memory as assessed by the N-Back, task as compared between patients receiving placebo vs those receiving L-Dopa. Earlier studies have shown a significant difference in accuracy and reaction time in a 2-back task, between patients with schizophrenia and healthy controls (Schneider et al., 2007; Karch et al, 2009). By adding L-dopa to antipsychotic treatment, we aim to improve the working memory of patients with schizophrenia with about 50%. Based on the effect sizes found in previous studies (Schneider et al., 2007; Karch et al., 2009), a power analysis shows that in order to show a 50% improvement in working memory, we would need to include approximately 40 patients. The third primary outcome measure is the improvement in negative symptoms as assessed by the PANSS negative symptoms subscale. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 0, 1, 2, 3, and 6 weeks |
|
E.5.2 | Secondary end point(s) |
Secondary outcome measures are change in positive symptoms as assessed by the PANSS positive symptoms score, the improvement in cognitive functions other than verbal memory and working memory, as assessed by the MATRICS, potential changes in frontal functions as assessed by the FAB, decrease of extrapyramidal symptoms as assessed by the ESRS, improvement in general functioning as assessed by the HoNOS, and CGI, and improvement of subjective wellbeing as assessed by the SWN. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
PANSS, MATRICS, and ESRS: at 0,1,2,3, and 6 weeks
HoNOS: at 0, 1, and 6 weeks
FAB, CGI, and SWN: at 0 and 6 weeks |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
rct on the efficacy of L-dopa addition to haloperidol or risperidone |
|
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
last visit of the last subject undergoing the trial |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |