Effects of Erythropoietin for Cognitive Side-effects of ECT

NCT03339596 | Completed Phase 2 DMC

• 3 other identifiers: H-16038506RHP-2017-0232016-002326-36
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

ECT; Cognitive Impairment; Unipolar Depression; Bipolar Depression

Keywords

electroconvulsive therapy; depression; cognition; cognitive side-effects; erythropoietin; functional magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

• 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.).

  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)

  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)

  Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion

Other Outcomes (9)

• Rey Auditory Verbal Learning Test (RAVLT)

  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

  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"

  Baseline, week 4 (i.e., after the last EPO injection and 8th ECT session), and 3 months after ECT treatment completion

Study Arms (2)

Erythropoietin

EXPERIMENTAL

4 intravenous infusions of recombinant human erythropoietin (EPO)

Drug: Erythropoietin

Saline

PLACEBO COMPARATOR

4 intravenous infusions of saline (1 ml NaCl)

Drug: Saline

Interventions

Erythropoietin DRUG

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.

Also known as: Eprex, EPO

Erythropoietin

Saline DRUG

1 ml NaCl is administered 4 times as intravenous infusions over 15 minutes

Also known as: Placebo

Saline

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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‰

Sponsors & Collaborators

• Martin Balslev Jørgensen: lead
• The Augustinus Foundation, Denmark.: collaborator
• Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital: collaborator

Study Sites (1)

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

Copenhagen, Copenhagen O, 2100, Denmark

Location

Related Publications (2)

• 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.

  PMID: 38128460 DERIVED

• Schmidt 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.

  PMID: 29673379 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Depressive Disorder; Bipolar Disorder; Depression

Interventions

Erythropoietin; Epoetin Alfa; Sodium Chloride

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Behavioral Symptoms; Behavior

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; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Martin B. Jørgensen, Prof.

  Psychiatric Centre Copenhagen, Rigshospitalet

  PRINCIPAL INVESTIGATOR

• Kamilla W. Miskowiak, Prof.

  Psychiatric Centre Copenhagen, Rigshospitalet

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 24, 2017
• First Posted: November 13, 2017
• Study Start: June 26, 2017
• Primary Completion: January 10, 2023
• Study Completion: February 10, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)