E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bipolar disorder and unipolar depression |
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E.1.1.1 | Medical condition in easily understood language |
Bipolar disorder (depression and mania) and depression |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057667 |
E.1.2 | Term | Bipolar disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045543 |
E.1.2 | Term | Unipolar depression |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 |
The main objective is to investigate the effect of 12 weeks of erythropoietin (EPO) treatment on cognitive impairments in patients with bipolar disorder or depression in remission with cognitive difficulties |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to investigate whether an early change in neural activity in prefrontal cortex correlates with and predicts improvements of cognitive functions in patients with bipolar disorder or depression in remission with cognitive difficulties |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with bipolar disorder or unipolar depression in remission:
• Bipolar disorder or unipolar depression confirmed with Schedules for Clinical Assessment in Neuropsychiatry (SCAN)-interview • 18-65 years of age • Score <=14 on Hamilton Depression Rating Scale 17 items (HDRS-17) and Young Mania Rating Scale (YMRS) • Cognitive difficulties assessed with the Danish version of the Screen for Cognitive Impairment in Psychiatry (SCIP), defined as a summed score of <=77 or score below cutoff on at least 2/5 subtests (list learning <=21, consonant trigramme task <=18, verbal fluency <=14, delayed list recall <=6, and visuomotor task <=10) on the SCIP-D (Jensen et al., 2015; Purdon, 2005) at the time of inclusion. Cutoff-scores are determined for each subtest in Jensen et al. (2015).
Participants must have adequate levels of Danish language skills to participate in the study. |
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E.4 | Principal exclusion criteria |
Previous EPO-treatment Drug abuse or addiction (including alcohol and benzodiazepines corresponding to >22.5 mg. alopam per day) Kidney disease Diabetes Pregnancy or breast feeding Women, who use the contraceptive pill or other hormonal contraceptives (not including hormonal coil) and do not want to use hormonal coil, copper coil or double barrier anticontraceptive methods Sexually active women in the fertile age, who do not or do not want to use hormonal coil, copper coil or double barrier anticontraceptive methods Previous head trauma Neurological illness Smoking Heart diseases (previously diagnosed or abnormal EKG findings during screening) Previous or current epilepsy in the participants or his/her first degree family Previous or current tromboembolic events or tromboses in first degree family occured before the age of 60 (because of increased tromboembolic risk) Contraindications against profylactic trombosis treatment Myeloproliferative disorder, polycythemia Obesity (BMI > 30) or a body weight of <45 kg or >95 kg Major surgical treatment within 4 weeks before inclusion in the study Known allergy to or antibodies against EPO Previous or current cancer disease Untreated or insufficiently treated hypertension ("therapy resistant hypertension" defined as a blood pressure over 140/90 mmHg; mean of 3 measures with 2 minute interval morning/midday and evening for three days) Baseline hematocrit value >50% for men and >48% for women Thrombocyte numbers over normal (>400 billions/L) Reticulocyte numbers ERC(B), below 1*10^-3 Reluctance or inability to comply with the protocol requirements, including the presence of any condition (physical, mental or social), which is likely to affect the participant's ability to comply with the protocol Current somatic disease, which is evaluated as being of importance for patient participation Electroconvulsive (ECT) treatment within the last 3 months Dyslexia Claustrophobia Pacemaker or metal implantate in the body Insufficient Danish language skills |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in the change of:
(i) A collected measure of cognition (a composite score) encompassing the following measures: Rey Auditory Verbal Learning Test – Total Recall (RAVLT; Schmidt, 2004), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding (Randolph, 1998), verbal fluency (with letter "D"; Borkowski, Benton, & Spreen, 1967), WAIS-III Letter-Number Sequencing (Wechsler, 1997), Trail Making Test Part B (TMT-B; Army Individual Test Battery, 1944), and Rapid Visual Processing (RVP) from Cambridge Neuropsychological Test Automated Battery (CANTAB), which cover attention, verbal learning and memory, and executive functions. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary end points will be evaluated at baseline (week 1), week 3 (2 weeks after treatment initiation), week 13 (1 week after treatment ending), and at 6 months follow-up |
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E.5.2 | Secondary end point(s) |
Difference in the change of:
(i) Cognition (attention and processing speed) measured with Rapid Visual Processing (RVP; CANTAB)
(ii) Function and quality of life measured with: the Functional Assessment Short Test (FAST; Rosa et al 2007) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary end points will be evaluated at baseline (week 1), week 3 (2 weeks after treatment initiation), week 13 (1 week after treatment ending), and at 6 months follow-up |
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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 | No |
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 | No |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
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
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The study will be completed by the end of juli 2022 (7-31-22) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 31 |