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

NCT ID: NCT00916552

Last Updated: 2012-11-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

83 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-30

Study Completion Date

2012-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Mood Disorders

Keywords

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Erythropoietin Epo depression bipolar disorder cognition cognitive function antidepressant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Erythropoeitin

40.000 IU, epoetin alfa; Janssen-Cilag

Group Type EXPERIMENTAL

Erythropoietin

Intervention Type DRUG

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

Interventions

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Erythropoietin

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

Intervention Type DRUG

Other Intervention Names

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Eprex Epo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Ministry of Science, Technology and Innovation, Denmark

OTHER_GOV

Sponsor Role collaborator

Novo Nordisk A/S

INDUSTRY

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role collaborator

Max-Planck-Institute of Experimental Medicine

OTHER

Sponsor Role collaborator

Lars Vedel Kessing, professor, MD, DMSc.

OTHER

Sponsor Role lead

Responsible Party

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Lars Vedel Kessing, professor, MD, DMSc.

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Lars V Kessing, Professor

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Locations

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Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status

Countries

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Denmark

References

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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.

Reference Type DERIVED
PMID: 31804779 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27835716 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27259062 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26996196 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26011424 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25641635 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25099079 (View on PubMed)

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.

Reference Type DERIVED
PMID: 20942940 (View on PubMed)

Other Identifiers

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EPO1

Identifier Type: -

Identifier Source: org_study_id