ECTPhase 2EPO-TNCT03339596
Effects of Erythropoietin for Cognitive Side-effects of ECT
A Phase 2 study testing Erythropoietin and Saline in people with ECT and Cognitive Impairment, run by Martin Balslev Jørgensen at 1 site in Denmark.
Trial summary
EPO-T aims to investigate (i) whether short-term add-on treatment with erythropoietin (EPO) can reduce cognitive side-effects of ECT and (ii) whether such effects are long-lasting. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- ECT, Cognitive Impairment, Unipolar Depression
- What is being tested?
- Erythropoietin and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteDenmark
- Study dates
- 26 Jun 2017to 10 Feb 2023
- 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
- ICD-10 diagnosis of major depressive disorder/unipolar disorder or bipolar disorder (confirmed using the Mini International Neuropsychiatric Interview; M.I.N.I.) with current moderate to severe depressive episode symptoms
- Hamilton Depression Rating Scale 17-items score ≥17
- Fluent Danish skills
Who cannot join
- Treatment under involuntary measures
- Other neuropsychiatric conditions
- Alcohol or substance misuse disorder
- Recent suicide attempts
- Diabetes
- Kidney disease
Show all 24Show fewer
- Renal failure
- Untreated/insufficiently treated arterial hypertension
- Heart diseases (previously diagnosed or abnormal ECG findings during screening)
- Previous or current epilepsy in patient or first degree family
- Malignancies or thromboses
- Known allergy or antibodies against erythropoietin
- Initial hematocrit > 50% (males) or > 48% (females)
- Initial thrombocyte numbers over normal (>400 billions/L)
- Initial reticulocyte numbers <1‰
- Contraindications against prophylactic thrombosis treatment
- Myeloproliferative disorder, polycythemia
- Pregnancy or breast feeding
- Use of contraceptive medication or other hormonal contraceptives
- Sexually active women in the fertile age, who do not or do not want to use double barrier anticontraceptive methods
- Previous or current history of thromboembolic events or thromboses in patient or first degree family (increased risk of thromboembolic events)
- Overweight (BMI>30) or body weight <45 or >95 kg.
- Previous electroconvulsive therapy (ECT) treatment within last 3 months
- Reluctance or inability to comply with the protocol requirements
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Mental Health Services, Capital Region of Denmark, Copenhagen University Hospital, Rigshospitalet
Copenhagen, Copenhagen O, 2100
About this study
Official title: Erythropoietin as an add-on Treatment for Cognitive Side-effects of Electroconvulsive Therapy
EPO-T aims to investigate (i) whether short-term add-on treatment with erythropoietin (EPO) can reduce cognitive side-effects of ECT and (ii) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings of such beneficial effects of EPO. Finally, the trial examines whether potential protective effects of EPO on cognition are accompanied by changes in markers of oxidative stress, inflammation, and neuroplasticity.
It is hypothesized that EPO treatment will (i) counteract ECT-induced cognitive decline, accompanied by (ii) increased sub-regional hippocampal volume, (iii) greater memory-related hippocampal activation and reinforcement of dorsolateral prefrontal activity during memory encoding and working memory, and (iv) changes in peripheral markers of inflammation, oxidative stress and neuroplasticity. Furthermore, we hypothesize that add-on EPO-treatment will produce greater, more sustained mood improvement than ECT treatment alone.
Read the detailed description
The trial will include patients with a diagnosis of major depression (MDD) unipolar disorder (UD) or bipolar disorder (BD) with a current moderate to severe depressive episode symptoms (a score of >17 on the Hamilton Depression Rating Scale 17-items (HRDS-17) scheduled for ECT treatment. Patients will be recruited from Psychiatric Centres in The Mental Health Services in the Capital Region of Denmark and will undergo an eligibility assessment prior to randomization to 4 intravenous infusions of either recombinant human EPO (40.000 IU/ml; Epoetin alpha; Eprex, Janssen-Cilag) or placebo (1 ml NaCl) diluted with 100 ml saline (0.9% NaCl).
Cognitive functions, mood symptoms, and blood- and urine markers of inflammation, oxidative stress, and neuroplasticity will be assessed 3 times during the trial. First time at baseline, second time 3 days after ECT session 8 (patients skip one ECT session day after 8 ECTs to minimise the confounding effects of acute side-effects of ECT due to anaesthesia etc.), and the third time at a 3 month follow-up after ECT completion. In addition, the neuronal substrates for potential effects of EPO on cognition are investigated with structural and functional MRI after 8 ECT sessions (after 3 weekly EPO or saline infusions).
Block randomization and power calculations have been conducted by the independent Pharma Consulting Group AB (www.pharmaconsultinggroup.com). Treatment groups are stratified for age (>40 or <40) and gender.
The difference in cognitive change between EPO and saline-treated groups from baseline to post-treatment in our previous trial was 0.5 SD. Based on these findings, the sample size of N=52 (n=26 per group) in the current trial will reach a >0.8 power to detect a clinically relevant difference in the primary outcome measure (the cognitive composite score) between the 2 groups at an alpha level of 5% (two-sided test). The study is also powered to investigate differences in functional magnetic resonance imaging (fMRI) blood-oxygen dependent level (BOLD) response in key neural networks based on previous fMRI studies from our group in which sample sizes of 30 age and gender matched participants (n=15 per group) had the power of >0.8 to show drug-related effects on task-related neural response at an alpha level of p<0.05. In the current trial, inclusion of 52 participants (n=26 per treatment group) therefore ensures sufficient statistical power to detect EPO-related effects on neural activity.
Behavioural, mood, and biomarker data will be analysed using Mixed Models Design and Intention to Treat (ITT) approaches. Resting state and task-related fMRI data will be pre-processed and analyzed using FMRIB Expert Analysis Tool (FEAT) and the 'randomize' algorithm integrated in FSL, FMRIB Software Library (www.fmrib.ox.ac.uk/fsl).
- Conditions
- ECT, Cognitive Impairment, Unipolar Depression, Bipolar Depression
- Being tested
- Erythropoietin, Saline
- Keywords
- electroconvulsive therapy, depression, cognition, cognitive side-effects, erythropoietin, functional magnetic resonance imaging
- Medical subject headings
- Cognitive Dysfunction, Depressive Disorder, Bipolar Disorder, Depression
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 Erythropoietin (Epoetin alpha; Eprex) diluted with 100 ml saline (0.9% NaCl) is administered 4 times as intravenous infusions over 15 minutes.
SalineDrug
Also called Placebo
1 ml NaCl is administered 4 times as intravenous infusions over 15 minutes
| Study group | Role | What they receive |
|---|---|---|
| Erythropoietin | Experimental | 4 intravenous infusions of recombinant human erythropoietin (EPO) Receives: Drug: Erythropoietin |
| Saline | Placebo comparator | 4 intravenous infusions of saline (1 ml NaCl) Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive composite score
A cognitive composite score based on an average of the Rey Auditory Verbal Learning Test (RAVLT), The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding, Verbal Fluency with the letter "D", Wechsler Adult Intelligence Scale (WAIS)-III Letter-Number Sequencing, Trail Making Test Part B, and Rapid Visual Information Processing (RVP) from the Cambridge Neuropsychological Test Automated Battery (CANTAB Cognition Ltd.).
Measured: Change from baseline to week 4 (i.e., after the last EPO injection and 8th ECT session)
Secondary outcomes (2)
Autobiographical Memory Interview-Short Form (AMI-SF)
Neuropsychological test assessing retrograde autobiographical memory
Measured: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Rey Auditory Verbal Learning Test (RAVLT)
Neuropsychological test assessing verbal learning and memory
Measured: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2017
- Study start26 Jun 2017
- Primary completion10 Jan 2023
- Study completion10 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ECTStudies 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Martin Balslev Jørgensen
- Sponsor type
- University, hospital or other
- Collaborators
- The Augustinus Foundation, Denmark., Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital
- Responsible party
- Sponsor-investigator, Martin Balslev Jørgensen, Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital
- Investigators
- Martin B. Jørgensen, Prof., Principal investigator, Psychiatric Centre Copenhagen, RigshospitaletKamilla W. Miskowiak, Prof., Study director, Psychiatric Centre Copenhagen, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03339596
- Sponsor's protocol ID
- H-16038506
- Other IDs
- RHP-2017-023, 2016-002326-36, 2016
- Acronym
- EPO-T
- Status last verified
- Sep 2023
- First submitted
- 24 Oct 2017
- Last updated
- 21 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Miskowiak KW, Petersen JZ, Macoveanu J, Ysbaek-Nielsen AT, Lindegaard IA, Cramer K, Mogensen MB, Hammershoj LG, Stougaard ME, Jorgensen JL, Schmidt LS, Vinberg M, Ehrenreich H, Hageman I, Videbech P, Gbyl K, Kellner CH, Kessing LV, Jorgensen MB. Effect of erythropoietin on cognitive side-effects of electroconvulsive therapy in depression: A randomized, double-blind, placebo-controlled trial. Eur Neuropsychopharmacol. 2024 Feb;79:38-48. doi: 10.1016/j.euroneuro.2023.12.004. Epub 2023 Dec 20.
PubMed 38128460Schmidt LS, Petersen JZ, Vinberg M, Hageman I, Olsen NV, Kessing LV, Jorgensen MB, Miskowiak KW. Erythropoietin as an add-on treatment for cognitive side effects of electroconvulsive therapy: a study protocol for a randomized controlled trial. Trials. 2018 Apr 19;19(1):234. doi: 10.1186/s13063-018-2627-2.
PubMed 29673379
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Erythropoietin as an add-on Treatment for Cognitive Side-effects of Electroconvulsive Therapy
- ClinicalTrials.gov ID
- NCT03339596
- Acronym / sponsor ID
- EPO-T / H-16038506
- Conditions
- ECT, Cognitive Impairment, Unipolar Depression, Bipolar Depression
- Keywords
- electroconvulsive therapy, depression, cognition, cognitive side-effects, erythropoietin, functional magnetic resonance imaging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Martin Balslev JørgensenUniversity, hospital or other
- Collaborators
- The Augustinus Foundation, Denmark., Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital
- Study start
- 26 Jun 2017 (actual)
- Primary completion
- 10 Jan 2023 (actual)
- Study completion
- 10 Feb 2023 (actual)
- First posted
- 13 Nov 2017 (actual)
- 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.
EPO-T aims to investigate (i) whether short-term add-on treatment with erythropoietin (EPO) can reduce cognitive side-effects of ECT and (ii) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings of such beneficial effects of EPO. Finally, the trial examines whether potential protective effects of EPO on cognition are accompanied by changes in markers of oxidative stress, inflammation, and neuroplasticity.
It is hypothesized that EPO treatment will (i) counteract ECT-induced cognitive decline, accompanied by (ii) increased sub-regional hippocampal volume, (iii) greater memory-related hippocampal activation and reinforcement of dorsolateral prefrontal activity during memory encoding and working memory, and (iv) changes in peripheral markers of inflammation, oxidative stress and neuroplasticity. Furthermore, we hypothesize that add-on EPO-treatment will produce greater, more sustained mood improvement than ECT treatment alone.
Detailed description
The trial will include patients with a diagnosis of major depression (MDD) unipolar disorder (UD) or bipolar disorder (BD) with a current moderate to severe depressive episode symptoms (a score of >17 on the Hamilton Depression Rating Scale 17-items (HRDS-17) scheduled for ECT treatment. Patients will be recruited from Psychiatric Centres in The Mental Health Services in the Capital Region of Denmark and will undergo an eligibility assessment prior to randomization to 4 intravenous infusions of either recombinant human EPO (40.000 IU/ml; Epoetin alpha; Eprex, Janssen-Cilag) or placebo (1 ml NaCl) diluted with 100 ml saline (0.9% NaCl).
Cognitive functions, mood symptoms, and blood- and urine markers of inflammation, oxidative stress, and neuroplasticity will be assessed 3 times during the trial. First time at baseline, second time 3 days after ECT session 8 (patients skip one ECT session day after 8 ECTs to minimise the confounding effects of acute side-effects of ECT due to anaesthesia etc.), and the third time at a 3 month follow-up after ECT completion. In addition, the neuronal substrates for potential effects of EPO on cognition are investigated with structural and functional MRI after 8 ECT sessions (after 3 weekly EPO or saline infusions).
Block randomization and power calculations have been conducted by the independent Pharma Consulting Group AB (www.pharmaconsultinggroup.com). Treatment groups are stratified for age (>40 or <40) and gender.
The difference in cognitive change between EPO and saline-treated groups from baseline to post-treatment in our previous trial was 0.5 SD. Based on these findings, the sample size of N=52 (n=26 per group) in the current trial will reach a >0.8 power to detect a clinically relevant difference in the primary outcome measure (the cognitive composite score) between the 2 groups at an alpha level of 5% (two-sided test). The study is also powered to investigate differences in functional magnetic resonance imaging (fMRI) blood-oxygen dependent level (BOLD) response in key neural networks based on previous fMRI studies from our group in which sample sizes of 30 age and gender matched participants (n=15 per group) had the power of >0.8 to show drug-related effects on task-related neural response at an alpha level of p<0.05. In the current trial, inclusion of 52 participants (n=26 per treatment group) therefore ensures sufficient statistical power to detect EPO-related effects on neural activity.
Behavioural, mood, and biomarker data will be analysed using Mixed Models Design and Intention to Treat (ITT) approaches. Resting state and task-related fMRI data will be pre-processed and analyzed using FMRIB Expert Analysis Tool (FEAT) and the 'randomize' algorithm integrated in FSL, FMRIB Software Library (www.fmrib.ox.ac.uk/fsl).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Erythropoietin | Experimental | Drug: Erythropoietin4 intravenous infusions of recombinant human erythropoietin (EPO) |
| Saline | Placebo comparator | Drug: Saline4 intravenous infusions of saline (1 ml NaCl) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- ICD-10 diagnosis of major depressive disorder/unipolar disorder or bipolar disorder (confirmed using the Mini International Neuropsychiatric Interview; M.I.N.I.) with current moderate to severe depressive episode symptoms
- Hamilton Depression Rating Scale 17-items score ≥17
- Fluent Danish skills
Key exclusion criteria (24 listed)
- Treatment under involuntary measures
- Other neuropsychiatric conditions
- Alcohol or substance misuse disorder
- Recent suicide attempts
- Diabetes
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 Erythropoietin (Epoetin alpha; Eprex) diluted with 100 ml saline (0.9% NaCl) is administered 4 times as intravenous infusions over 15 minutes. | Drug | Erythropoietin |
| SalineAlso: Placebo1 ml NaCl is administered 4 times as intravenous infusions over 15 minutes | Drug | Saline |
Primary outcome
Cognitive composite score
Time frame: Change from baseline to week 4 (i.e., after the last EPO injection and 8th ECT session)
A cognitive composite score based on an average of the Rey Auditory Verbal Learning Test (RAVLT), The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding, Verbal Fluency with the letter "D", Wechsler Adult Intelligence Scale (WAIS)-III Letter-Number Sequencing, Trail Making Test Part B, and Rapid Visual Information Processing (RVP) from the Cambridge Neuropsychological Test Automated Battery (CANTAB Cognition Ltd.).
2 secondary outcomes
Autobiographical Memory Interview-Short Form (AMI-SF)
Time frame: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Rey Auditory Verbal Learning Test (RAVLT)
Time frame: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
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 21 Sep 2023.
- Derived from this study: PubMed 38128460Miskowiak KW, Petersen JZ, Macoveanu J, Ysbaek-Nielsen AT, Lindegaard IA, Cramer K, Mogensen MB, Hammershoj LG, Stougaard ME, Jorgensen JL, Schmidt LS, Vinberg M, Ehrenreich H, Hageman I, Videbech P, Gbyl K, Kellner CH, Kessing LV, Jorgensen MB. Effect of erythropoietin on cognitive side-effects of electroconvulsive therapy in depression: A randomized, double-blind, placebo-controlled trial. Eur Neuropsychopharmacol. 2024 Feb;79:38-48. doi: 10.1016/j.euroneuro.2023.12.004. Epub 2023 Dec 20.
- Derived from this study: PubMed 29673379Schmidt LS, Petersen JZ, Vinberg M, Hageman I, Olsen NV, Kessing LV, Jorgensen MB, Miskowiak KW. Erythropoietin as an add-on treatment for cognitive side effects of electroconvulsive therapy: a study protocol for a randomized controlled trial. Trials. 2018 Apr 19;19(1):234. doi: 10.1186/s13063-018-2627-2.
- Individual participant dataSharing planned: No
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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.
Martin B. Jørgensen, Prof. principal investigator
Psychiatric Centre Copenhagen, Rigshospitalet
Kamilla W. Miskowiak, Prof. study director
Psychiatric Centre Copenhagen, 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 and Saline in people with ECT and Cognitive Impairment, run by Martin Balslev Jørgensen 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 3 inclusion and 24 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 21 Sep 2023. 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. Some participants in this study may receive a placebo. 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?
Cognitive composite score (time frame: Change from baseline to week 4 (i.e., after the last EPO injection and 8th ECT session)). 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 NCT03339596, which also lists 2 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 21 Sep 2023.