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

NCT00916552 | Completed Phase 2 DMC

• 1 other identifier: EPO1
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mood Disorders

Keywords

Erythropoietin; Epo; depression; bipolar disorder; cognition; cognitive function; antidepressant

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• 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

Study Arms (1)

Erythropoeitin

EXPERIMENTAL

40.000 IU, epoetin alfa; Janssen-Cilag

Drug: Erythropoietin

Interventions

Erythropoietin DRUG

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

Also known as: Eprex, Epo

Erythropoeitin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

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

Study Sites (1)

Copenhagen University Hospital, Rigshospitalet

Copenhagen, 2200, Denmark

Location

Related Publications (8)

• Miskowiak KW, Forman JL, Vinberg M, Siebner HR, Kessing LV, Macoveanu J. Impact of pretreatment interhemispheric hippocampal asymmetry on improvement in verbal learning following erythropoietin treatment in mood disorders: a randomized controlled trial. J Psychiatry Neurosci. 2020 May 1;45(3):198-205. doi: 10.1503/jpn.180205.

  PMID: 31804779 DERIVED

• Miskowiak KW, Rush AJ Jr, Gerds TA, Vinberg M, Kessing LV. Targeting Treatments to Improve Cognitive Function in Mood Disorder: Suggestions From Trials Using Erythropoietin. J Clin Psychiatry. 2016 Dec;77(12):e1639-e1646. doi: 10.4088/JCP.15m10480.

  PMID: 27835716 DERIVED

• Miskowiak KW, Macoveanu J, Vinberg M, Assentoft E, Randers L, Harmer CJ, Ehrenreich H, Paulson OB, Knudsen GM, Siebner HR, Kessing LV. Effects of erythropoietin on memory-relevant neurocircuitry activity and recall in mood disorders. Acta Psychiatr Scand. 2016 Sep;134(3):249-59. doi: 10.1111/acps.12597. Epub 2016 Jun 3.

  PMID: 27259062 DERIVED

• Miskowiak KW, Vinberg M, Glerup L, Paulson OB, Knudsen GM, Ehrenreich H, Harmer CJ, Kessing LV, Siebner HR, Macoveanu J. Neural correlates of improved executive function following erythropoietin treatment in mood disorders. Psychol Med. 2016 Jun;46(8):1679-91. doi: 10.1017/S0033291716000209. Epub 2016 Mar 21.

  PMID: 26996196 DERIVED

• Vinberg M, Miskowiak K, Hoejman P, Pedersen M, Kessing LV. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders: a randomised controlled study. PLoS One. 2015 May 26;10(5):e0127629. doi: 10.1371/journal.pone.0127629. eCollection 2015.

  PMID: 26011424 DERIVED

• Miskowiak KW, Vinberg M, Macoveanu J, Ehrenreich H, Koster N, Inkster B, Paulson OB, Kessing LV, Skimminge A, Siebner HR. Effects of Erythropoietin on Hippocampal Volume and Memory in Mood Disorders. Biol Psychiatry. 2015 Aug 15;78(4):270-7. doi: 10.1016/j.biopsych.2014.12.013. Epub 2014 Dec 18.

  PMID: 25641635 DERIVED

• Miskowiak KW, Ehrenreich H, Christensen EM, Kessing LV, Vinberg M. Recombinant human erythropoietin to target cognitive dysfunction in bipolar disorder: a double-blind, randomized, placebo-controlled phase 2 trial. J Clin Psychiatry. 2014 Dec;75(12):1347-55. doi: 10.4088/JCP.13m08839.

  PMID: 25099079 DERIVED

• Miskowiak KW, Vinberg M, Harmer CJ, Ehrenreich H, Knudsen GM, Macoveanu J, Hansen AR, Paulson OB, Siebner HR, Kessing LV. Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder. Trials. 2010 Oct 13;11:97. doi: 10.1186/1745-6215-11-97.

  PMID: 20942940 DERIVED

MeSH Terms

Conditions

Mood Disorders; Depression; Bipolar Disorder

Interventions

Erythropoietin; Epoetin Alfa; Eosinophil Peroxidase

Condition Hierarchy (Ancestors)

Mental Disorders; Behavioral Symptoms; Behavior; Bipolar and Related Disorders

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Peroxidases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Eosinophil Granule Proteins; Immunoproteins; Blood Proteins

Study Officials

• Lars V Kessing, Professor

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 8, 2009
• First Posted: June 9, 2009
• Study Start: September 1, 2009
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: November 9, 2012

Record last verified: 2012-11

Locations

DK (1)