Effects of Erythropoietin on Depressive Symptoms and Neurocognitive Deficits in Depression and Bipolar Disorder

Mood Disorders Clinical Trial

Official title:

The Effects of Erythropoietin on Depressive Symptoms and Neurocognitive Deficits in Patients With Treatment Resistant Depression and in Patients With Remitted Bipolar Disorder - a Proof of Concept Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00916552
• Other study ID #: EPO1
• Status: Completed
• Phase: Phase 2
• First received: June 8, 2009
• Last updated: November 8, 2012
• Start date: September 2009
• Est. completion date: October 2012

Study information

• Verified date: November 2012
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Depression and bipolar disorder (mania and depression) may be related to problems with nerve cells not being regenerated as fast as normal and are accompanied by cognitive difficulties including memory, attention and planning problems. There is thus a need for better, more efficient treatments with effects on cognitive function. Erythropoietin (Epo) is involved in brain repair and may be a candidate for future treatment strategies. The investigators have demonstrated that a single dose of Epo improves mood and reduces the processing of negative emotional information in healthy volunteers similar to effects seen with antidepressants. With the current study the investigators aim to build upon this discovery by investigating whether repeated Epo administration has antidepressant effects and is able to reverse cognitive difficulties in patients with depression or bipolar disorder. It is hypothesized that Epo will improve mood in treatment-resistant depression and improve cognitive function in this group and in patients with bipolar disorder in remission. If the study reveals beneficial effects of Epo, this would highlight Epo as a candidate compound for future treatment of depression and bipolar disorder, with the potential to directly promote brain repair mechanisms.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Treatment-resistant depression (defined as failure to respond to at least 2 different types of antidepressants) and an HDRS score of at least 17

OR

• Bipolar disorder in remission (HDRS score of max 14 and Young Mania Scale score of max 14) and subjective complaints of moderate to severe cognitive problems on the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) (Fava et al 2006) (score at least 4 on at least 2 domains)

• Unchanged antidepressant or mood stabilizing treatment for at least 2 weeks prior to and during the study

Exclusion Criteria:

• Schizophrenia/ schizoaffective disorder

• Dependence on or abuse of drugs (including alcohol and benzodiazepines corresponding to more than 22.5 mg Oxazepam daily)

• Diabetes

• Renal failure

• Smoking

• Major surgery within 4 weeks prior to inclusion

• Previous Epo-treatment

• Known allergy or antibodies against Epo

• Present or past malignancies

• Epilepsy or epilepsy in first degree family Diagnosis (past or present) of a cardiovascular or cerebrovascular disease

• Untreated or not sufficiently treated arterial hypertension ("therapy-resistant hypertension")

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

• Initial platelet count above normal range of laboratory

• Initial reticulocyte count below norma range of laboratory

• Past thromboembolic events or thromboembolic events in first degree family (increased thromboembolic risk)

• Contraindications against prophylactic thrombosis treatment

• Myeloproliferative disorder, polycythemia

• Present immunosuppressive treatment with cyclosporin

• Overweight (BMI > 30) or body weight of less than 45 kg or over 95 kg

• Acute suicidal risk, present or previous suicide attempts in the past 2 years

• Pregnancy or breast feeding

• Women who presently use contraceptive pills

• Sexually active women with child bearing potential who refuse to use double barrier anticonception methods

• Unwillingness or inability to comply with the requirements of the protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the protocol

• Present illness which in investigator's opinion could affect the patient's participation in the study

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder
• Depressive Disorder, Treatment-Resistant
• Mood Disorders

Intervention

Drug:
• Erythropoietin
40.000 IU/ml epoetin alfa is administered as intravenous infusions over 15 min weekly for 8 weeks.

Locations

Country	Name	City	State
Denmark	Copenhagen University Hospital, Rigshospitalet	Copenhagen

Sponsors (5)

Lead Sponsor	Collaborator
Lars Vedel Kessing, professor, MD, DMSc.	Max-Planck-Institute of Experimental Medicine, Novo Nordisk A/S, The Ministry of Science, Technology and Innovation, Denmark, University of Oxford

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	a) For treatment-resistant depressed patients: Antidepressant effect measured with the Hamilton Depression Rating Scale (HDRS); b) For bipolar patients in remission: Memory measured with the Rey Auditory Verbal Memory Test.		a) Baseline and weeks 5, 9 and 14; b) Baseline and weeks 9 and 14	No
Secondary	a) For treatment-resistant depressed patients: number of remissions measured with the HDRS; b) For bipolar patients in remission: sustained attention measured with the RVIP and facial expression recognition.		a) Baseline and weeks 5, 9 and 14; b) Baseline and weeks 9 and 14	No