Mood DisordersPhase 2NCT00916552
Effects of Erythropoietin on Depressive Symptoms and Neurocognitive Deficits in Depression and Bipolar Disorder
A Phase 2 study testing Erythropoietin in people with Mood Disorders, run by Lars Vedel Kessing, professor, MD, DMSc. at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Mood Disorders
- What is being tested?
- Erythropoietin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 1 siteDenmark
- Study dates
- Sep 2009to Oct 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 25Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- Erythropoietin
- Keywords
- Erythropoietin, Epo, depression, bipolar disorder, cognition, cognitive function, antidepressant
- Medical subject headings
- Mood Disorders, Depression, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErythropoietinDrug
Also called Eprex, Epo
40.000 IU/ml epoetin alfa is administered as intravenous infusions over 15 min weekly for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Erythropoeitin | Experimental | 40.000 IU, epoetin alfa; Janssen-Cilag Receives: Drug: Erythropoietin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: a) Baseline and weeks 5, 9 and 14; b) Baseline and weeks 9 and 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2009 (estimated)
- Study startSep 2009
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Mood DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lars Vedel Kessing, professor, MD, DMSc.
- Sponsor type
- University, hospital or other
- Collaborators
- The Ministry of Science, Technology and Innovation, Denmark, Novo Nordisk A/S, University of Oxford, Max-Planck-Institute of Experimental Medicine
- Responsible party
- Sponsor-investigator, Lars Vedel Kessing, professor, MD, DMSc., Copenhagen University Hospital, Rigshospitalet
- Investigators
- Lars V Kessing, Professor, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00916552
- Sponsor's protocol ID
- EPO1
- Status last verified
- Nov 2012
- First submitted
- 8 Jun 2009
- Last updated
- 9 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 31804779Miskowiak 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.
PubMed 27835716Miskowiak 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.
PubMed 27259062Miskowiak 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.
PubMed 26996196Vinberg 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.
PubMed 26011424Miskowiak 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.
PubMed 25641635Miskowiak 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.
PubMed 25099079Miskowiak 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.
PubMed 20942940
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00916552
- Acronym / sponsor ID
- EPO1
- Conditions
- Mood Disorders
- Keywords
- Erythropoietin, Epo, depression, bipolar disorder, cognition, cognitive function, antidepressant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Lars Vedel Kessing, professor, MD, DMSc.University, hospital or other
- Collaborators
- The Ministry of Science, Technology and Innovation, Denmark, Novo Nordisk A/S, University of Oxford, Max-Planck-Institute of Experimental Medicine
- Study start
- Sep 2009
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 9 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erythropoeitin | Experimental | Drug: Erythropoietin40.000 IU, epoetin alfa; Janssen-Cilag |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErythropoietinAlso: Eprex, Epo40.000 IU/ml epoetin alfa is administered as intravenous infusions over 15 min weekly for 8 weeks. | Drug | Erythropoeitin |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2012.
- Derived from this study: PubMed 31804779Miskowiak 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.
- Derived from this study: PubMed 27835716Miskowiak 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.
- Derived from this study: PubMed 27259062Miskowiak 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.
- Derived from this study: PubMed 26996196Miskowiak 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.
- Derived from this study: PubMed 26011424Vinberg 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.
- Derived from this study: PubMed 25641635Miskowiak 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.
- Derived from this study: PubMed 25099079Miskowiak 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.
- Derived from this study: PubMed 20942940Miskowiak 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lars V Kessing, Professor principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Erythropoietin in people with Mood Disorders, run by Lars Vedel Kessing, professor, MD, DMSc. at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00916552, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2012.