Effects of Erythropoietin for Cognitive Side-effects of ECT (EPO-T)

September 18, 2023 updated by: Martin Balslev Jørgensen

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Denmark
    • Copenhagen O
      • Copenhagen, Copenhagen O, Denmark, 2100
        • Mental Health Services, Capital Region of Denmark, Copenhagen University Hospital, Rigshospitalet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Treatment under involuntary measures
  • Other neuropsychiatric conditions
  • Alcohol or substance misuse disorder
  • Recent suicide attempts
  • Diabetes
  • Kidney disease
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Erythropoietin
4 intravenous infusions of recombinant human erythropoietin (EPO)
Drug: Erythropoietin
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.
Other Names:
  • EPO
  • Eprex
Placebo Comparator: Saline
4 intravenous infusions of saline (1 ml NaCl)
Drug: Saline
1 ml NaCl is administered 4 times as intravenous infusions over 15 minutes
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.).
Change from baseline to week 4 (i.e., after the last EPO injection and 8th ECT session)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Neuropsychological test assessing retrograde autobiographical memory
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
Neuropsychological test assessing verbal learning and memory
Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Neuropsychological test assessing verbal learning and memory
Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding
Time Frame: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Neuropsychological test assessing attention
Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Verbal Fluency with the letter "D"
Time Frame: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Neuropsychological test assessing executive functions
Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Wechsler Adult Intelligence Scale (WAIS)-III Letter-Number Sequencing
Time Frame: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Neuropsychological test assessing executive functions
Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Trail Making Test Part B
Time Frame: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Neuropsychological test assessing executive functions
Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Rapid Visual Information Processing (RVP) from the Cambridge Neuropsychological Test Automated Battery (CANTAB Cognition Ltd.)
Time Frame: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Neuropsychological test assessing sustained attention
Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Hamilton Depression Rating Scale 17-items Version
Time Frame: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Clinician-based interview assessing depression severity
Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Beck Depression Inventory 21-items
Time Frame: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Questionnaire assessing subjectively-rated depression severity
Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Cognitive Complaints in Bipolar Disorder Rating Assessment
Time Frame: Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion
Questionnaire assessing subjectively-rated cognitive complaints
Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Martin Balslev Jørgensen

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Mental Health Services in the Capital Region, Denmark
The Augustinus Foundation, Denmark.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Martin B. Jørgensen, Prof., Psychiatric Centre Copenhagen, Rigshospitalet
  • Study Director: Kamilla W. Miskowiak, Prof., Psychiatric Centre Copenhagen, Rigshospitalet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 26, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 10, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 10, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 24, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 9, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 13, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 21, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 18, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • H-16038506
  • RHP-2017-023 (Other Identifier: The Danish Data Protection Agency Capital Region of Denmark)
  • 2016-002326-36 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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