Effects of Erythropoietin on Cognition and Neural Activity in Mood Disorders

• Status: Recruiting
• Trial end date: 2021-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The present trial consists of 2 sub-studies that investigate important novel aspects of treatment with erythropoietin (EPO) on cognitive dysfunction in bipolar disorder (BD) and recurrent unipolar depressive disorder (UD) (defined as minimum 2 treatment-requiring depressive episodes). The aims of the trial are three-fold. We aim to investigate the effects of 12 weekly recombinant human EPO infusions on cognition in (i) healthy people with cognitive impairment (substudy 1) and (ii) patients with remitted BD or recurrent UD (substudy 2), and (iii) explore early treatment-associated neural activity changes that may predict subsequent cognitive improvement.

It is hypothesized that:

i. 12 weekly EPO infusions improve cognition in healthy first-degree relatives and remitted BD patients in comparison with saline.

ii. EPO vs. saline-treated participants will display early cognition-related neural activity in the frontal lobes, which will correlate with cognitive improvement.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Lars Vedel Kessing
• Collaborators: Lundbeck Foundation; Mental Health Services in the Capital Region, Denmark
• Treatments: Epoetin Alfa

Criteria

Inclusion Criteria:

• Fluent Danish skills and objective cognitive impairment (a total score below cutoff, or scores below cutoff on a minimum of two out of the five subtests (Verbal Learning Test - Immediate, Working Memory Test, Verbal Fluency Test, Verbal Learning Test - Delayed and Processing Speed Test) on the Screen for Cognitive Impairment in Psychiatry - Danish version (SCIP-D).

• Patients must meet the ICD-10 diagnosis of BD (type I and II) or recurrent depressive disorder confirmed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview.

• Healthy people are eligible even when diagnosed with a less severe mental disorder defined as ICD-10 codes ≥F40.

Exclusion Criteria:

• Schizophrenia or schizoaffective disorder

• Current alcohol or substance misuse disorder (3 months prior to inclusion)

• Daily use of benzodiazepines > 22.5 mg oxazepam

• Diabetes

• Kidney disease

• Renal failure

• Untreated/insufficiently treated arterial hypertension

• Heart diseases (previously diagnosed or abnormal ECG findings during screening)

• Previous serious head trauma

• Neurological illness (including dementia)

• Previous or current epilepsy in patient or first degree family

• Malignancies or thromboses

• Known allergy or antibodies against erythropoietin

• Initial hematocrit > 50% (males) or > 48% (females)

• Initial thrombocyte numbers over normal (>400 billions/L)

• Initial reticulocyte numbers <1‰

• Contraindications against prophylactic thrombosis treatment

• Myeloproliferative disorder, polycythemia

• Pregnancy or breast feeding

• Use of contraceptive medication or other hormonal contraceptives

• Sexually active women in the fertile age, who do not or do not want to use double barrier anticontraceptive methods

• Previous or current history of thromboembolic events or thromboses in patient or first degree family (increased risk of thromboembolic events)

• Overweight (BMI>30) or body weight <45 or >95 kg.

• Previous electroconvulsive therapy (ECT) treatment within last 3 months

• Dyslexia

• Claustrophobia

• Having a pacemaker or other metal implants inside the body

• Reluctance or inability to comply with the protocol requirements