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

This study has been completed.
Sponsor:
Collaborators:
The Ministry of Science, Technology and Innovation, Denmark
Novo Nordisk A/S
University of Oxford
Max-Planck-Institute of Experimental Medicine
Information provided by (Responsible Party):
Lars Vedel Kessing, professor, MD, DMSc., Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT00916552
First received: June 8, 2009
Last updated: November 8, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Mood Disorders
Drug: Erythropoietin
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • 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. [ Time Frame: a) Baseline and weeks 5, 9 and 14; b) Baseline and weeks 9 and 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: a) Baseline and weeks 5, 9 and 14; b) Baseline and weeks 9 and 14 ] [ Designated as safety issue: No ]

Enrollment: 83
Study Start Date: September 2009
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erythropoeitin
40.000 IU, epoetin alfa; Janssen-Cilag
Drug: Erythropoietin
40.000 IU/ml epoetin alfa is administered as intravenous infusions over 15 min weekly for 8 weeks.
Other Names:
  • Eprex
  • Epo

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00916552

Locations
Denmark
Copenhagen University Hospital, Rigshospitalet
Copenhagen, Denmark, 2200
Sponsors and Collaborators
Lars Vedel Kessing, professor, MD, DMSc.
The Ministry of Science, Technology and Innovation, Denmark
Novo Nordisk A/S
University of Oxford
Max-Planck-Institute of Experimental Medicine
Investigators
Principal Investigator: Lars V Kessing, Professor Rigshospitalet, Denmark
  More Information

No publications provided by Rigshospitalet, Denmark

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Lars Vedel Kessing, professor, MD, DMSc., Professor, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT00916552     History of Changes
Other Study ID Numbers: EPO1
Study First Received: June 8, 2009
Last Updated: November 8, 2012
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: Ethics Committee

Keywords provided by Rigshospitalet, Denmark:
Erythropoietin
Epo
depression
bipolar disorder
cognition
cognitive function
antidepressant

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Mood Disorders
Affective Disorders, Psychotic
Mental Disorders
Behavioral Symptoms
Epoetin Alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014