Effects of Erythropoietin on Cognition and Neural Activity in Mood Disorders

NCT03315897 | Completed Phase 2 DMC

• 3 other identifiers: H-160433702016-004023-24RHP-2017-020
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

The present trial consists of 2 sub-studies that investigate important novel aspects of treatment with erythropoietin (EPO) on cognitive dysfunction in bipolar disorder (BD) and recurrent unipolar depressive disorder (UD) (defined as minimum 2 treatment-requiring depressive episodes). The aims of the trial are three-fold. We aim to investigate the effects of 12 weekly recombinant human EPO infusions on cognition in (i) healthy people with cognitive impairment (substudy 1) and (ii) patients with remitted BD or recurrent UD (substudy 2), and (iii) explore early treatment-associated neural activity changes that may predict subsequent cognitive improvement. It is hypothesized that: i. 12 weekly EPO infusions improve cognition in healthy first-degree relatives and remitted BD patients in comparison with saline. ii. EPO vs. saline-treated participants will display early cognition-related neural activity in the frontal lobes, which will correlate with cognitive improvement.

Conditions

Bipolar Disorder; Cognitive Impairment; Unipolar Depression

Keywords

bipolar disorder; cognition; cognitive dysfunction; erythropoietin; pro-cognitive efficacy; prefrontal cortex; functional magnetic resonance imaging; biomarker; unipolar disorder

Outcome Measures

Primary Outcomes (1)

• Cognitive composite score

  A cognitive composite based on an average of the Rey Auditory Verbal Learning Test (RAVLT), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding, verbal fluency with the letter "D", WAIS-III Letter-Number Sequencing, Trail Making Test B (TMT B) and Rapid Visual Information Processing (RVP) from Cambridge Cognition (CANTAB).

  Change from baseline and week 13

Secondary Outcomes (2)

• Rapid Visual Information Processing (RVP) from Cambridge Cognition (CANTAB)

  Baseline, two weeks of treatment, week 13, and 6-months follow-up

• Functional Assessment Short Test

  Baseline, week 13, and 6-months follow-up

Other Outcomes (15)

• Rey Auditory Verbal Learning Test

  Baseline, two weeks of treatment, week 13, and 6-months follow-up

• Trail Making Test Part A

  Baseline, two weeks of treatment, week 13, and 6-months follow-up

• Trail Making Test Part B

  Baseline, two weeks of treatment, week 13, and 6-months follow-up

Study Arms (2)

Erythropoietin

ACTIVE COMPARATOR

12 intravenous infusions of recombinant human erythropoietin (EPO)

Drug: Erythropoietin

Saline

PLACEBO COMPARATOR

12 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 12 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: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fluent Danish skills and objective cognitive impairment (a total score below cutoff, or scores below cutoff on a minimum of two out of the five subtests (Verbal Learning Test - Immediate, Working Memory Test, Verbal Fluency Test, Verbal Learning Test - Delayed and Processing Speed Test) on the Screen for Cognitive Impairment in Psychiatry - Danish version (SCIP-D).
• Patients must meet the ICD-10 diagnosis of BD (type I and II) or recurrent depressive disorder confirmed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview.
• Healthy people are eligible even when diagnosed with a less severe mental disorder defined as ICD-10 codes ≥F40.

You may not qualify if:

• Schizophrenia or schizoaffective disorder
• Daily use of benzodiazepines \> 22.5 mg oxazepam
• Diabetes
• Kidney disease
• Renal failure
• Untreated/insufficiently treated arterial hypertension
• Heart diseases (previously diagnosed or abnormal ECG findings during screening)
• Previous serious head trauma
• Neurological illness (including dementia)
• 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

• Lars Vedel Kessing: lead
• Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital: collaborator
• Lundbeck Foundation: collaborator

Study Sites (1)

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

Copenhagen, 2100, Denmark

Location

Related Publications (2)

• Macoveanu J, Petersen JZ, Mariegaard J, Jespersen AE, Cramer K, Bruun CF, Madsen HO, Jorgensen MB, Vinberg M, Fisher PM, Knudsen GM, Hageman I, Ehrenreich H, Kessing LV, Miskowiak KW. Effects of erythropoietin on cognitive impairment and prefrontal cortex activity across affective disorders: A randomized, double-blinded, placebo-controlled trial. J Psychopharmacol. 2024 Apr;38(4):362-374. doi: 10.1177/02698811241237869. Epub 2024 Mar 22.

  PMID: 38519416 DERIVED

• Petersen JZ, Schmidt LS, Vinberg M, Jorgensen MB, Hageman I, Ehrenreich H, Knudsen GM, Kessing LV, Miskowiak KW. Effects of recombinant human erythropoietin on cognition and neural activity in remitted patients with mood disorders and first-degree relatives of patients with psychiatric disorders: a study protocol for a randomized controlled trial. Trials. 2018 Nov 6;19(1):611. doi: 10.1186/s13063-018-2995-7.

  PMID: 30400939 DERIVED

MeSH Terms

Conditions

Bipolar Disorder; Cognitive Dysfunction; Depressive Disorder

Interventions

Erythropoietin; Epoetin Alfa; Sodium Chloride

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

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

• Lars V. Kessing, Prof.

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

  PRINCIPAL INVESTIGATOR

• Kamilla W. Miskowiak, Prof.

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

  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, MD, DMSc

Study Record Dates

• First Submitted: October 17, 2017
• First Posted: October 20, 2017
• Study Start: July 5, 2017
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: March 16, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)