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
Abstract Background Bipolar disorder (BD) and unipolar disorder (UD) are associated with cognitive deficits and abnormal neural activity in a “cognitive control network.” There is an increased prevalence of cognitive dysfunction in psychiatric patients’ first-degree relatives, which constitutes a ri...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-11-01
|
| Series: | Trials |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13063-018-2995-7 |
| _version_ | 1818689110456401920 |
|---|---|
| author | Jeff Zarp Petersen Lejla Sjanic Schmidt Maj Vinberg Martin Balslev Jørgensen Ida Hageman Hannelore Ehrenreich Gitte Moos Knudsen Lars Vedel Kessing Kamilla Woznica Miskowiak |
| author_facet | Jeff Zarp Petersen Lejla Sjanic Schmidt Maj Vinberg Martin Balslev Jørgensen Ida Hageman Hannelore Ehrenreich Gitte Moos Knudsen Lars Vedel Kessing Kamilla Woznica Miskowiak |
| author_sort | Jeff Zarp Petersen |
| collection | DOAJ |
| description | Abstract Background Bipolar disorder (BD) and unipolar disorder (UD) are associated with cognitive deficits and abnormal neural activity in a “cognitive control network.” There is an increased prevalence of cognitive dysfunction in psychiatric patients’ first-degree relatives, which constitutes a risk factor for psychiatric illness onset. However, there is no treatment with enduring pro-cognitive efficacy. We found preliminary evidence for beneficial effects of eight weekly doses of recombinant human erythropoietin (EPO) on cognition in BD in a recent randomized controlled trial (RCT). The present RCT consists of two sub-studies that extend our previous work by investigating important novel aspects: (1) the effects of 12 weekly doses of EPO on cognition in first-degree relatives of patients with BD, UD, or schizophrenia; and (2) the effects of extending the treatment schedule from 8 to 12 weeks in remitted patients with BD or UD; and (3) assessment of early treatment-associated neural activity changes that may predict cognitive improvement. Methods The trial comprises two parallel sub-studies with randomized, controlled, double-blinded, parallel group designs. First-degree relatives (sub-study 1; n = 52) and partially or fully remitted patients with BD or UD (sub-study 2; n = 52) with objectively verified cognitive dysfunction are randomized to receive weekly high-dose EPO (40,000 IU/mL) or placebo (saline) infusions for 12 weeks. Assessments of cognition and mood are conducted at baseline, after two weeks of treatment, after treatment completion, and at six-month follow-up. Functional magnetic resonance imaging (fMRI) is conducted at baseline and after two weeks of treatment. Psychosocial function is assessed at baseline, after treatment completion and six-month follow-up. The primary outcome is change in a cognitive composite score of attention, verbal memory, and executive functions. Statistical power of ≥ 80% is reached to detect a clinically relevant between-group difference by including 52 first-degree relatives and 52 patients with BD or UD, respectively. Behavioral data are analyzed with an intention-to-treat approach using mixed models. fMRI data are analyzed with the FMRIB Software Library. Discussion If this trial reveals pro-cognitive effects of EPO, this may influence future treatment of mood disorders and/or preventive strategies in at-risk populations. The fMRI analyses may unravel key neurobiological targets for pro-cognitive treatment. Trial registration ClinicalTrials.gov, NCT03315897. Registered on 20 October 2017. |
| first_indexed | 2024-12-17T12:04:54Z |
| format | Article |
| id | doaj.art-58e05e816f264a04a2a0cb30a6090434 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-17T12:04:54Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-58e05e816f264a04a2a0cb30a60904342022-12-21T21:49:41ZengBMCTrials1745-62152018-11-0119111410.1186/s13063-018-2995-7Effects 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 trialJeff Zarp Petersen0Lejla Sjanic Schmidt1Maj Vinberg2Martin Balslev Jørgensen3Ida Hageman4Hannelore Ehrenreich5Gitte Moos Knudsen6Lars Vedel Kessing7Kamilla Woznica Miskowiak8Neurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University HospitalNeurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University HospitalNeurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University HospitalNeurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University HospitalNeurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University HospitalClinical Neuroscience, Max Planck Institute of Experimental MedicineNeurobiology Research Unit and Center for Integrated Molecular Imaging, RigshospitaletNeurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University HospitalNeurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University HospitalAbstract Background Bipolar disorder (BD) and unipolar disorder (UD) are associated with cognitive deficits and abnormal neural activity in a “cognitive control network.” There is an increased prevalence of cognitive dysfunction in psychiatric patients’ first-degree relatives, which constitutes a risk factor for psychiatric illness onset. However, there is no treatment with enduring pro-cognitive efficacy. We found preliminary evidence for beneficial effects of eight weekly doses of recombinant human erythropoietin (EPO) on cognition in BD in a recent randomized controlled trial (RCT). The present RCT consists of two sub-studies that extend our previous work by investigating important novel aspects: (1) the effects of 12 weekly doses of EPO on cognition in first-degree relatives of patients with BD, UD, or schizophrenia; and (2) the effects of extending the treatment schedule from 8 to 12 weeks in remitted patients with BD or UD; and (3) assessment of early treatment-associated neural activity changes that may predict cognitive improvement. Methods The trial comprises two parallel sub-studies with randomized, controlled, double-blinded, parallel group designs. First-degree relatives (sub-study 1; n = 52) and partially or fully remitted patients with BD or UD (sub-study 2; n = 52) with objectively verified cognitive dysfunction are randomized to receive weekly high-dose EPO (40,000 IU/mL) or placebo (saline) infusions for 12 weeks. Assessments of cognition and mood are conducted at baseline, after two weeks of treatment, after treatment completion, and at six-month follow-up. Functional magnetic resonance imaging (fMRI) is conducted at baseline and after two weeks of treatment. Psychosocial function is assessed at baseline, after treatment completion and six-month follow-up. The primary outcome is change in a cognitive composite score of attention, verbal memory, and executive functions. Statistical power of ≥ 80% is reached to detect a clinically relevant between-group difference by including 52 first-degree relatives and 52 patients with BD or UD, respectively. Behavioral data are analyzed with an intention-to-treat approach using mixed models. fMRI data are analyzed with the FMRIB Software Library. Discussion If this trial reveals pro-cognitive effects of EPO, this may influence future treatment of mood disorders and/or preventive strategies in at-risk populations. The fMRI analyses may unravel key neurobiological targets for pro-cognitive treatment. Trial registration ClinicalTrials.gov, NCT03315897. Registered on 20 October 2017.http://link.springer.com/article/10.1186/s13063-018-2995-7Bipolar disorderDepressionCognitionCognitive dysfunctionErythropoietinPro-cognitive efficacy |
| spellingShingle | Jeff Zarp Petersen Lejla Sjanic Schmidt Maj Vinberg Martin Balslev Jørgensen Ida Hageman Hannelore Ehrenreich Gitte Moos Knudsen Lars Vedel Kessing Kamilla Woznica Miskowiak 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 Bipolar disorder Depression Cognition Cognitive dysfunction Erythropoietin Pro-cognitive efficacy |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Bipolar disorder Depression Cognition Cognitive dysfunction Erythropoietin Pro-cognitive efficacy |
| url | http://link.springer.com/article/10.1186/s13063-018-2995-7 |
| work_keys_str_mv | AT jeffzarppetersen effectsofrecombinanthumanerythropoietinoncognitionandneuralactivityinremittedpatientswithmooddisordersandfirstdegreerelativesofpatientswithpsychiatricdisordersastudyprotocolforarandomizedcontrolledtrial AT lejlasjanicschmidt effectsofrecombinanthumanerythropoietinoncognitionandneuralactivityinremittedpatientswithmooddisordersandfirstdegreerelativesofpatientswithpsychiatricdisordersastudyprotocolforarandomizedcontrolledtrial AT majvinberg effectsofrecombinanthumanerythropoietinoncognitionandneuralactivityinremittedpatientswithmooddisordersandfirstdegreerelativesofpatientswithpsychiatricdisordersastudyprotocolforarandomizedcontrolledtrial AT martinbalslevjørgensen effectsofrecombinanthumanerythropoietinoncognitionandneuralactivityinremittedpatientswithmooddisordersandfirstdegreerelativesofpatientswithpsychiatricdisordersastudyprotocolforarandomizedcontrolledtrial AT idahageman effectsofrecombinanthumanerythropoietinoncognitionandneuralactivityinremittedpatientswithmooddisordersandfirstdegreerelativesofpatientswithpsychiatricdisordersastudyprotocolforarandomizedcontrolledtrial AT hanneloreehrenreich effectsofrecombinanthumanerythropoietinoncognitionandneuralactivityinremittedpatientswithmooddisordersandfirstdegreerelativesofpatientswithpsychiatricdisordersastudyprotocolforarandomizedcontrolledtrial AT gittemoosknudsen effectsofrecombinanthumanerythropoietinoncognitionandneuralactivityinremittedpatientswithmooddisordersandfirstdegreerelativesofpatientswithpsychiatricdisordersastudyprotocolforarandomizedcontrolledtrial AT larsvedelkessing effectsofrecombinanthumanerythropoietinoncognitionandneuralactivityinremittedpatientswithmooddisordersandfirstdegreerelativesofpatientswithpsychiatricdisordersastudyprotocolforarandomizedcontrolledtrial AT kamillawoznicamiskowiak effectsofrecombinanthumanerythropoietinoncognitionandneuralactivityinremittedpatientswithmooddisordersandfirstdegreerelativesofpatientswithpsychiatricdisordersastudyprotocolforarandomizedcontrolledtrial |