Ignite Creation Date:
2024-05-06 @ 8:23 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06367907
Status:
RECRUITING
Last Update Posted:
2024-04-16
First Post:
2024-03-08
Brief Title:
Biological Effects of Schema Therapy
Sponsor:
Jena University Hospital
Organization:
Jena University Hospital
Study Overview
Official Title:
Effects of Emotion-focused vs Cognitive Schema Therapy Interventions on Emotion Regulation Deficits in Borderline Personality Disorder - Associations Between Clinical Efficacy Brain Network Function and Local GlutamateGABA Metabolism
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BE-ST
Brief Summary:
Background The major aim of this study is to compare the effects of emotion focused experiential and cognitive interventions of schema therapy ST on emotion regulation deficits in patients with borderline personality disorder BPD according to DSM-V alternative model criteria In a randomized single-blinded parallel-group design clinical effects as well as effects on neurotransmitter metabolism and connectivity will be compared
Method While the 9-weeks treatment protocol of particular interest includes emotion focused interventions ST-EF n60 such as chair dialogs imagery rescripting or role play the active control condition ST-AC n60 is restricted to cognitive interventions eg psychoeducation or procontra discussions MEGA-PRESS 1H-MR spectroscopy and resting-state functional MR imaging rs-fMRI will be used beforeafter treatment protocols T0-T1 and 6 months after the end of therapy T2 to assess the effects on glutamate Glx and GABA metabolism in key regions of the target networks executive control network ECN dorsolateral prefrontal cortex DLPFC salience network SN anteromedial cingulate cortex aMCC default mode network DMN pregenual cingulate cortex pgACC and to investigate the corresponding altered connectivity in these networks The biological aberrations at T0 as compared to healthy controls n60 and treatment effects at T1 and T2 n40 in each condition on these aberrations will be linked to clinical effects measured by an extensive test battery with particular interest on emotion regulation and specified by the Reliable Change Index RCI For longitudinal data mixed model analysis will be performed
The main questions are 1 whether the emotion regulation deficit and the pattern of BPD-specific symptomatology are associated with a specific pattern of Glx and GABA concentrations in the DLPFC aMCC and pgACC and corresponding deviations of functional connectivity within the ECN SN and DMN Hypothesis Depending on primary and secondary outcome measures at T0 altered RSFC in the DMN SN and ECN and corresponding altered Glx or GABA concentrations are assumed 2 whether both treatment conditions have different clinical effects on the ability to regulate emotions and whether the respective clinical effects are associated with the changes in neurobiological aberrations Hypothesis It is hypothesized that the ST-EF condition will improve emotion regulation skills more effectively than the control condition Only in the ST-EF condition are higher response and remission rates expected in the primary and secondary outcome measures as well as effects on the ECN SN and DMN with corresponding changes in RSFC and Glx or GABA concentrations
Method While the 9-weeks treatment protocol of particular interest includes emotion focused interventions ST-EF n60 such as chair dialogs imagery rescripting or role play the active control condition ST-AC n60 is restricted to cognitive interventions eg psychoeducation or procontra discussions MEGA-PRESS 1H-MR spectroscopy and resting-state functional MR imaging rs-fMRI will be used beforeafter treatment protocols T0-T1 and 6 months after the end of therapy T2 to assess the effects on glutamate Glx and GABA metabolism in key regions of the target networks executive control network ECN dorsolateral prefrontal cortex DLPFC salience network SN anteromedial cingulate cortex aMCC default mode network DMN pregenual cingulate cortex pgACC and to investigate the corresponding altered connectivity in these networks The biological aberrations at T0 as compared to healthy controls n60 and treatment effects at T1 and T2 n40 in each condition on these aberrations will be linked to clinical effects measured by an extensive test battery with particular interest on emotion regulation and specified by the Reliable Change Index RCI For longitudinal data mixed model analysis will be performed
The main questions are 1 whether the emotion regulation deficit and the pattern of BPD-specific symptomatology are associated with a specific pattern of Glx and GABA concentrations in the DLPFC aMCC and pgACC and corresponding deviations of functional connectivity within the ECN SN and DMN Hypothesis Depending on primary and secondary outcome measures at T0 altered RSFC in the DMN SN and ECN and corresponding altered Glx or GABA concentrations are assumed 2 whether both treatment conditions have different clinical effects on the ability to regulate emotions and whether the respective clinical effects are associated with the changes in neurobiological aberrations Hypothesis It is hypothesized that the ST-EF condition will improve emotion regulation skills more effectively than the control condition Only in the ST-EF condition are higher response and remission rates expected in the primary and secondary outcome measures as well as effects on the ECN SN and DMN with corresponding changes in RSFC and Glx or GABA concentrations
Detailed Description:
23 Work program and proposed research methods
The work program is divided into the following three work packages
1 Recruitment of patients and healthy subjects including diagnostic and psychological assessments as well as assessment of clinical outcome
2 Collecting the MR-related Glx GABA RSFC
3 Data evaluation and analysis of the results
Recruitment of patients and healthy subjects Patients will be recruited from routine admissions to the psychiatric day-hospital According to our power calculation we aim to include at least 120 patients with BPD according to the general and borderline specific criteria of the alternative DSM-5 Model for Personality Disorders Section III of DSM 5 p 761ff APA 2013 which includes a specific dimensional pattern of impairments in personality functioning and pathological personality traits for diagnosis
A total of at least 60 healthy volunteers will be recruited by newspaper advertisement They will be examined using a semi-structured interview and self-ratings SCL-90-R to assess current mental status to exclude personal or first-degree family history of psychiatric disorders including substance abuse or history of neurological or major medical conditions that might affect brain function
Description of therapy conditions withwithout emotion focused schema therapy interventions
Deficits in emotion regulation are widely seen as a core pathology in BPD Hence quicker and more intense emotional activation can a priori be expected in every BPD patient This study makes use of the fact that some interventions in ST evoke intense emotions child modes eg to foster awareness of childs needs while others aim to establish a healthy distance from overintense emotions to enable adequate parental care healthy adult mode With regard to emotions schema therapy techniques have been divided into therapy relationship experiential cognitive and behavioral techniques Fassbinder et al 2016 Schem therapy assumes that by using these strategies the patients fear of emotions reduces while willingness to overcome experiential avoidance increases Fassbinder et al 2016 This approach also clarifies old biographically linked goals of emotion regulation behavior now counting as dysfunctional or a strategies of emotional avoidance now replacing them by new actual goals that require and enhance new functional emotion regulation behavior
MR-based investigation protocol
Scheduled acquisitions scan time including patient positioning up to 15h
High-resolution T1-weighted 3D whole brain scan using the MP-RAGE sequence TRTETI 2530271100 ms α 7 176 sagittal slices of 1 mm thickness FOVAPHF 256 256 mm² in-plane matrix 256 256 pixels acquisition time 6 min
Resting state fMRI scan of the entire brain using T2-weighted EPI TRTE 252030 ms whole brain coverage with 45 transverse slices thickness 25 mm FoVAPLR 220210 mm² in-plane matrix 8884 pixels 240 volumes TA 10 min
1H-MR spectra with MEGA-PRESS sequence in three voxels placed in the aMCC SN network and left and right DLPFC ECN network
Manual adjustment of field homogeneity and water suppression 5 min TRTE 200068 ms 256 alternating single acquisitions with subsequent application of frequency-selective RF pulses at 19 ppm and 75 ppm respectively additional series acquisition of twelve water non-suppressed single scans with varying echo times TR 20 s TEs 30 40 50 60 75 90 110 150 175 200 250 300 ms TA 17 min per voxel total MRS duration of 50 - 55 min
Photoplethysmogram PPG and respiration recordings during MRI acquisition with 500 Hz using an MR-compatible polygraph MP150 BIOPAC Systems Inc Goleta CA USA Respiratory activity will be monitored by a strain gauge transducer incorporated in a belt tied around the chest approximately at the level of the xiphoid process The PPG sensor will be attached to the proximal phalanx of the left index finger
Analysis of baseline T0 MRI-data
Separate analysis for rs-fMRI and 1H-MRS data
A seed-based correlation analysis will be used to explore the whole-brain RSFC pattern of the regions being central to the study ie the aMCC and DLPFC Analysis of variance ANOVA will be applied to test for RSFC differences between patient groups and controls
The same analyses will be applied to analyze group differences of the local Glx and GABA concentrations as well as the GlxGABA balance in aMCC and DLPFC between patients and controls
Associations between rs-fMRI and 1H-MRS data
A linear mixed model analysis will be performed to investigate differences of associations between RSFC SN and ECN and Glx or GABA concentrations at the aMCC and DLPFC between patients and controls
Follow-up T0-T1T1-T2 analysis of treatment effects on MRI target parameters RSFC Glx GABA
Separated analysis for rs-fMRI and 1H-MRS data
Analysis of variance ANOVA for repeated measures will be applied to test for effects of group belonging ST-EF ST-AC and healthy subjects ST-EF vs ST-AC on changes of RSFC Glx and GABA over time as well as for within-subject changes between T0 and T1 and T1 and T2 scans
Associations between RSFC and the local Glx and GABA concentrations
A linear mixed model analysis will be performed to investigate changes after 9 weeks of treatment T0 vs T1 or 6month of catamnesis T1 vs T2 of either therapeutic condition ST-EF ST-AC compared to unspecific changes over time in healthy controls as well as between treatment groups
In a first step this analysis will be performed separately in both treatment groups and healthy controls and for both neurotransmitters Glx GABA and both spectroscopic and functional connectivity target regions aMCC DLPFC
In the second more important step potential treatment condition driven differences in the correlations between metabolic and RSFC parameters will be investigated by applying the same model including the factor treatment group
Clinical outcome
Evaluation of changes of core symptoms and their clinical significance
In a follow-up T0-T1 T1-T2 analysis of treatment effects the individual change of each patient in measures of the primary Emotion Regulation Inventory ERI and secondary Borderline Personality Disorder Severity Index - fourth version BPDSI-IV Levels of Personality Functioning Scale SEFP Personality Inventory for DSM-5 Criterion B PID-5 Borderline Symptom List 95 Items BSL-95 Inventory of Interpersonal Problems IIP-D Young Schema Questionnaire short version YSQ-S3r and Schema Mode Inventory 118 item version SMI outcome criteria will be estimated by the Reliable Change Index RCI Wise 2004 in each therapeutic condition
Evaluation of changes in primary and secondary criteria and their clinical significance In each therapeutic condition the improvement of each patient in measures of the primary ERI and secondary BPDSI-IV SEFP PID-5 BSL-95 IIP-D YSQ-S3r and SMI outcome criteria will be estimated by the Reliable Change Index RCI which summarizes changes at the level of an individual in the context of observed changes for the whole sample
The RCI provides information about the functioning of an individual beforeafter therapy on an outcome measure including the normative information about this measure by dividing the difference between pre- and post-treatment scores by the standard error that includes also the reliability coefficient not only the standard deviation of the measure The change will be considered as being unlikely the product of measurement error ie considered reliable if the RCI is greater than 196 When the individual has a change score greater than 196 it can be assumed that the individual has improved More detailed information on RCI scores and their meaning in each outcome measurement is given in the uploaded material
Interrelation between clinical outcome parameters and neurobiological findings
A linear mixed model analysis will be used that includes those MRI-data RSFC Glx GABA that have been significantly affected by therapy T0 vs T1 and those clinical scores that reached the highest RCI The detected significant interactions will be compared between the ST-EF and ST-AC treatment condition
The work program is divided into the following three work packages
1 Recruitment of patients and healthy subjects including diagnostic and psychological assessments as well as assessment of clinical outcome
2 Collecting the MR-related Glx GABA RSFC
3 Data evaluation and analysis of the results
Recruitment of patients and healthy subjects Patients will be recruited from routine admissions to the psychiatric day-hospital According to our power calculation we aim to include at least 120 patients with BPD according to the general and borderline specific criteria of the alternative DSM-5 Model for Personality Disorders Section III of DSM 5 p 761ff APA 2013 which includes a specific dimensional pattern of impairments in personality functioning and pathological personality traits for diagnosis
A total of at least 60 healthy volunteers will be recruited by newspaper advertisement They will be examined using a semi-structured interview and self-ratings SCL-90-R to assess current mental status to exclude personal or first-degree family history of psychiatric disorders including substance abuse or history of neurological or major medical conditions that might affect brain function
Description of therapy conditions withwithout emotion focused schema therapy interventions
Deficits in emotion regulation are widely seen as a core pathology in BPD Hence quicker and more intense emotional activation can a priori be expected in every BPD patient This study makes use of the fact that some interventions in ST evoke intense emotions child modes eg to foster awareness of childs needs while others aim to establish a healthy distance from overintense emotions to enable adequate parental care healthy adult mode With regard to emotions schema therapy techniques have been divided into therapy relationship experiential cognitive and behavioral techniques Fassbinder et al 2016 Schem therapy assumes that by using these strategies the patients fear of emotions reduces while willingness to overcome experiential avoidance increases Fassbinder et al 2016 This approach also clarifies old biographically linked goals of emotion regulation behavior now counting as dysfunctional or a strategies of emotional avoidance now replacing them by new actual goals that require and enhance new functional emotion regulation behavior
MR-based investigation protocol
Scheduled acquisitions scan time including patient positioning up to 15h
High-resolution T1-weighted 3D whole brain scan using the MP-RAGE sequence TRTETI 2530271100 ms α 7 176 sagittal slices of 1 mm thickness FOVAPHF 256 256 mm² in-plane matrix 256 256 pixels acquisition time 6 min
Resting state fMRI scan of the entire brain using T2-weighted EPI TRTE 252030 ms whole brain coverage with 45 transverse slices thickness 25 mm FoVAPLR 220210 mm² in-plane matrix 8884 pixels 240 volumes TA 10 min
1H-MR spectra with MEGA-PRESS sequence in three voxels placed in the aMCC SN network and left and right DLPFC ECN network
Manual adjustment of field homogeneity and water suppression 5 min TRTE 200068 ms 256 alternating single acquisitions with subsequent application of frequency-selective RF pulses at 19 ppm and 75 ppm respectively additional series acquisition of twelve water non-suppressed single scans with varying echo times TR 20 s TEs 30 40 50 60 75 90 110 150 175 200 250 300 ms TA 17 min per voxel total MRS duration of 50 - 55 min
Photoplethysmogram PPG and respiration recordings during MRI acquisition with 500 Hz using an MR-compatible polygraph MP150 BIOPAC Systems Inc Goleta CA USA Respiratory activity will be monitored by a strain gauge transducer incorporated in a belt tied around the chest approximately at the level of the xiphoid process The PPG sensor will be attached to the proximal phalanx of the left index finger
Analysis of baseline T0 MRI-data
Separate analysis for rs-fMRI and 1H-MRS data
A seed-based correlation analysis will be used to explore the whole-brain RSFC pattern of the regions being central to the study ie the aMCC and DLPFC Analysis of variance ANOVA will be applied to test for RSFC differences between patient groups and controls
The same analyses will be applied to analyze group differences of the local Glx and GABA concentrations as well as the GlxGABA balance in aMCC and DLPFC between patients and controls
Associations between rs-fMRI and 1H-MRS data
A linear mixed model analysis will be performed to investigate differences of associations between RSFC SN and ECN and Glx or GABA concentrations at the aMCC and DLPFC between patients and controls
Follow-up T0-T1T1-T2 analysis of treatment effects on MRI target parameters RSFC Glx GABA
Separated analysis for rs-fMRI and 1H-MRS data
Analysis of variance ANOVA for repeated measures will be applied to test for effects of group belonging ST-EF ST-AC and healthy subjects ST-EF vs ST-AC on changes of RSFC Glx and GABA over time as well as for within-subject changes between T0 and T1 and T1 and T2 scans
Associations between RSFC and the local Glx and GABA concentrations
A linear mixed model analysis will be performed to investigate changes after 9 weeks of treatment T0 vs T1 or 6month of catamnesis T1 vs T2 of either therapeutic condition ST-EF ST-AC compared to unspecific changes over time in healthy controls as well as between treatment groups
In a first step this analysis will be performed separately in both treatment groups and healthy controls and for both neurotransmitters Glx GABA and both spectroscopic and functional connectivity target regions aMCC DLPFC
In the second more important step potential treatment condition driven differences in the correlations between metabolic and RSFC parameters will be investigated by applying the same model including the factor treatment group
Clinical outcome
Evaluation of changes of core symptoms and their clinical significance
In a follow-up T0-T1 T1-T2 analysis of treatment effects the individual change of each patient in measures of the primary Emotion Regulation Inventory ERI and secondary Borderline Personality Disorder Severity Index - fourth version BPDSI-IV Levels of Personality Functioning Scale SEFP Personality Inventory for DSM-5 Criterion B PID-5 Borderline Symptom List 95 Items BSL-95 Inventory of Interpersonal Problems IIP-D Young Schema Questionnaire short version YSQ-S3r and Schema Mode Inventory 118 item version SMI outcome criteria will be estimated by the Reliable Change Index RCI Wise 2004 in each therapeutic condition
Evaluation of changes in primary and secondary criteria and their clinical significance In each therapeutic condition the improvement of each patient in measures of the primary ERI and secondary BPDSI-IV SEFP PID-5 BSL-95 IIP-D YSQ-S3r and SMI outcome criteria will be estimated by the Reliable Change Index RCI which summarizes changes at the level of an individual in the context of observed changes for the whole sample
The RCI provides information about the functioning of an individual beforeafter therapy on an outcome measure including the normative information about this measure by dividing the difference between pre- and post-treatment scores by the standard error that includes also the reliability coefficient not only the standard deviation of the measure The change will be considered as being unlikely the product of measurement error ie considered reliable if the RCI is greater than 196 When the individual has a change score greater than 196 it can be assumed that the individual has improved More detailed information on RCI scores and their meaning in each outcome measurement is given in the uploaded material
Interrelation between clinical outcome parameters and neurobiological findings
A linear mixed model analysis will be used that includes those MRI-data RSFC Glx GABA that have been significantly affected by therapy T0 vs T1 and those clinical scores that reached the highest RCI The detected significant interactions will be compared between the ST-EF and ST-AC treatment condition
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None