Clinical trial NCT01908855: Cognitive-Behavioral Therapy Enriched With Emotion Regulation Training for Multiple Somatoform Symptoms
Official title: Enriching Cognitive-Behavioral Therapy With Emotion Regulation Training in Patients With Chronic Multiple Somatoform Symptoms (ENCERT): A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Somatic Symptom Disorder (DSM-V)
Keywords: somatoform symptoms
somatic symptoms
somatoform disorder
somatic symptom disorder
cognitive-behavioral therapy
emotion regulation training
Lead sponsor: Philipps University Marburg
Sponsor class: OTHER
Collaborators: name: University of Technology Munich
name: Central Institute of Mental Health, Mannheim
name: University of Giessen
name: University of Wuppertal
name: Universitätsklinikum Hamburg-Eppendorf
name: University of Kaiserslautern-Landau
name: German Research Foundation
name: Philipps University Marburg Coordination Centre for Clinical Trials
First posted: 2013-07-26
Enrollment: 255
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate whether cognitive-behavioral therapy enriched with strategies from emotion regulation training leads to better improvement in somatic symptoms and comorbid problems than cognitive-behavioral therapy alone.

Detailed description: Somatic symptoms not caused by a known biomedical condition ("somatoform disorders") are highly prevalent, involve a high risk of chronicity, are one of the major reasons for doctor visits, and are a tremendous burden for health care systems. Despite the economic relevance, research activities are disproportionately low. The only intervention with an evidence grade I is cognitive-behavioral therapy (CBT). However, average effect sizes for CBT in somatization syndromes are only moderate (Cohen's d \< 0.5), and more powerful interventions are needed.

There is convincing evidence that patients with somatoform disorders have emotion regulation deficits, which are not addressed by current CBT approaches. Based on positive results of a small pilot study it is expected that enriching CBT programs with emotion regulation techniques improves treatment outcome. The primary goal of the proposed project is therefore to evaluate this hypothesis in a randomized design.

Patients will be primarily recruited via referrals by primary care doctors. After a screening phase a baseline assessments with different self- and clinician-rating scales (see Outcome Measures) follows. If participants fulfill the eligibility criteria they will be randomized to one of the two study arms: cognitive-behavioral therapy vs. cognitive-behavioral therapy enriched with emotion regulation strategies. After every therapy session patients will be screened in regard to aspects of therapeutic alliance, adverse events, and symptom intensity/annoyance. The post assessment takes place after the 20th session and a follow-up is planned six months after post treatment.

Different methods will be applied to prevent bias and to assure a high quality level of the current study. Data handling, data monitoring and statistical analyses will be supervised by the Coordinating Center for Clinical Trials (KKS) of Philipps-University of Marburg; data quality and safety principles will be applied. Additionally an independent Data Safety Monitoring Board will be nominated. The study center will visit all study sites regularly to verify correct procedures, data sampling, and data management. Randomisation occurs and is controlled centrally through the randomisation's central office in KKS Marburg. Furthermore the current study constitutes a single-blinded trial. Assessment interviews are conducted and analyzed by people blinded to the treatment condition. Additionally, treatments are manualized, and therapists receive an intense training. Treatment fidelity/integrity is analyzed with rating schemes for 5% randomly selected videotaped treatment sessions. Allowed additional treatments during study inclusion are thoroughly monitored and analyzed.

The sample size calculation is based on the primary outcome variable "somatization severity index" of the Screening of Somatoform Disorders (SOMS-7T). Based on results of the main validation study of SOMS-7T, meta-analytic estimations, and results of a pilot study of the efficacy of ENCERT, the power calculations yield a necessary total sample size of N=194 to detect a clinical relevant difference of 4 points symptom reduction on SOMS-7T between the two treatments with a power of 0.80 and an alpha=.05. With regard to an estimated drop-out rate of 20%, N=244 patients are to be recruited.

As main efficacy analysis the primary outcome shall be analyzed with linear mixed-effect models. It will be done according to the Intention-to-Treat (ITT) principle: to consider missing values as a potential source of bias, they will be handled according to the framework by Rubin. Secondary statistical analyses focus on establishing longer term treatment efficacy and describing the pattern of change. For this purpose the mean response will be modeled as a function of time with a separate mixed effects linear model over all assessments. Furthermore, interindividual differences in intraindividual change will be modeled using multilevel analysis for longitudinal data. Multilevel longitudinal mediation analyses will be conducted in order to test whether the effect of treatment condition on intraindividual changes in somatic symptom severity can be explained by intraindividual changes in emotion regulation skills.

Eligibility criteria: Inclusion Criteria (are based on DSM-V diagnosis "somatic symptom disorder \[SSD\] 300.82"):

* Multiple distressing somatic symptoms (≥ 3 symptoms) not fully explained by a medical condition
* PDI ≥ 4
* Patient Health Questionnaire-15 (PHQ-15) ≥ 5
* Requested psychological criteria for SSD (at least 1 of 3):

  1. Disproportionate and persistent thoughts about the seriousness of one's symptoms
  2. Persistently high level of anxiety about health or symptoms
  3. Excessive time and energy devoted to these symptoms or health concerns
* Symptom duration ≥ 6 months
* Age: 18-69 years
* Comorbidity (depression, other mental disorders) allowed, as long as somatic symptoms are considered to be the major problem by therapist and patient
* Thorough medical check for medical disease that might fully explain the somatic symptoms
* Documented medical evaluation

Exclusion Criteria:

* Severe alcohol/drug addiction
* Acquired brain injuries
* Psychoses (history of schizophrenia spectrum disorders; bipolar disorders)
* Primary disorder requesting other treatments (e.g., suicidality)
* Biomedical etiology of major symptoms (also if detected during treatment course
* Ongoing psychotherapy
* Continuous or intermittent, high-dosage (on average more than once per 2 weeks) benzodiazepine treatment
* Continuous antipsychotic treatment
* Continuous opioid treatment
* For patients on medication with antidepressants: treatment regime changes during the time between 4 weeks prior to treatment until follow-up

Primary outcomes:
measure: Change in somatic symptom severity (Screening of Somatoform Disorders, SOMS-7T) from pre-assessment to four in-between assessments to post-assessment to follow-up
timeFrame: From pre-assessment (admission) to four in-between assessments (9, 13, 17, 21 weeks after admission) to post-assessment (25 weeks after admission) to follow-up (12 months after admission)
Secondary outcomes:
measure: Change in depressive symptoms (Beck Depression Inventory-II, BDI-II) from pre-assessment to one in-between assessment to post-assessment to follow-up
timeFrame: From pre-assessment (admission) to one in-between assessment (13 weeks after admission) to post-assessment (25 weeks after admission) to follow-up (12 months after admission)
measure: Change in emotion regulation skills (Emotion Regulation Skills Questionnaire, ERSQ) from pre-assessment to one in-between assessment to post-assessment to follow-up
timeFrame: From pre-assessment (admission) to one in-between assessment (13 weeks after admission) to post-assessment (25 weeks after admission) to follow-up (12 months after admission)
measure: Change in symptom-focussed coping strategies (Pain Coping Questionnaire, FESV; Geissner, 2003) from pre-assessment to one in-between assessment to post-assessment to follow-up
timeFrame: From pre-assessment (admission) to one in-between assessment (13 weeks after admission) to post-assessment (25 weeks after admission) to follow-up (12 months after admission)
measure: Change in general psychopathological symptoms (Symptom Checklist-90, SCL-90) from pre-assessment to one in-between assessment to post-assessment to follow-up
timeFrame: From pre-assessment (admission) to one in-between assessment (13 weeks after admission) to post-assessment (25 weeks after admission) to follow-up (12 months after admission)
measure: Change in symptom-caused disability (Pain Disability Index, PDI) from pre-assessment to one in-between assessment to post-assessment to follow-up
timeFrame: From pre-assessment (admission) to one in-between assessment (13 weeks after admission) to post-assessment (25 weeks after admission) to follow-up (12 months after admission)
measure: Change in health-related quality of life (EuroQoL-5D, EQ-5D) from pre-assessment to one in-between assessment to post-assessment to follow-up
timeFrame: From pre-assessment (admission) to one in-between assessment (13 weeks after admission) to post-assessment (25 weeks after admission) to follow-up (12 months after admission)
measure: Change in health anxiety (Whiteley Index, WI) from pre-assessment to one in-between assessment to post-assessment to follow-up
timeFrame: From pre-assessment (admission) to one in-between assessment (13 weeks after admission) to post-assessment (25 weeks after admission) to follow-up (12 months after admission)
measure: Change in social competence, emotion regulation, relaxation abilities, stress management, etc., in different areas of life (The Operationalized Assessment of Abilities, OFD) from pre-assessment to post-assessment to follow-up
timeFrame: From pre-assessment (admission) to post-assessment (25 weeks after admission) to follow-up (12 months after admission)
measure: Change in health care utilization and indirect costs (Structured Interview for the Assessment of Health Care Utilization, HCU) from pre-assessment to follow-up
timeFrame: From pre-assessment (admission) to follow-up (12 months after admission)
measure: Inventory of the Assessment of Negative Effects of Psychotherapy (INEP) at post-assessment
timeFrame: Post-assessment (25 weeks after admission)
measure: Inventory of the Assessment of Negative Effects of Psychotherapy (INEP) at follow-up
timeFrame: Follow-up (12 months after admission)
Other outcomes:
Locations:
city: Gießen
country: Germany
facility: Justus-Liebig-University, CBT Outpatient Clinic
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf, Department of Psychosomatic Medicine
city: Koblenz-Landau
country: Germany
facility: University Koblenz-Landau, Department of Clinical Psychology and Psychotherapy
city: Mannheim
country: Germany
facility: Central Institute of Mental Health, Department of Clinical Psychology
city: Marburg
country: Germany
facility: Philipps-University, Department of Clinical Psychology and Psychotherapy
city: München
country: Germany
facility: Rechts der Isar Hospital, University of Technology, Department of Psychosomatic Medicine and Psychotherapy
city: Wuppertal
country: Germany
facility: Bergische University, Department of Clinical Psychology and Psychotherapy
Study officials:
affiliation: Philipps University Marburg
name: Winfried Rief, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Philipps University Marburg
name: Mathias Berking, Ph.D.
role: STUDY_CHAIR
affiliation: Philipps University Marburg
name: Maria Kleinstäuber, Ph.D.
role: STUDY_CHAIR
affiliation: Philipps University Marburg
name: Japhia-Maria Gottschalk, M.Sc.
role: STUDY_CHAIR
References:
citation: Barsky AJ, Orav EJ, Bates DW. Somatization increases medical utilization and costs independent of psychiatric and medical comorbidity. Arch Gen Psychiatry. 2005 Aug;62(8):903-10. doi: 10.1001/archpsyc.62.8.903.
citation: Geissner E. Pain Coping Questionnaire FESV. Göttingen, Germany: Hogrefe; 2003.
citation: Göllner R, Gollwitzer M, Heider J, Zaby A, Schröder A. Analyzing longitudinal data with hierarchical linear models. Zeitschrift für Klinische Psychologie und Psychotherapie 39(3):179-88, 2010.
citation: Gottschalk JM, Bleichhardt G, Kleinstäuber M, Berking M, Rief W. Treatment efficacy of multiple somatoform symptoms? Enriching cognitive behavioral therapy with emotion regulation training: Results of a controlled pilot study. In preparation.
citation: Jacobi F, Wittchen H-U, Holting C, Hofler M, Pfister H, Muller N, Lieb R. Prevalence, co-morbidity and correlates of mental disorders in the general population: results from the German Health Interview and Examination Survey (GHS). Psychol Med. 2004 May;34(4):597-611. doi: 10.1017/S0033291703001399.
citation: Kleinstauber M, Witthoft M, Hiller W. Efficacy of short-term psychotherapy for multiple medically unexplained physical symptoms: a meta-analysis. Clin Psychol Rev. 2011 Feb;31(1):146-60. doi: 10.1016/j.cpr.2010.09.001. Epub 2010 Sep 16.
citation: Kroenke K. Efficacy of treatment for somatoform disorders: a review of randomized controlled trials. Psychosom Med. 2007 Dec;69(9):881-8. doi: 10.1097/PSY.0b013e31815b00c4.
citation: Molenberghs G, Kenward MG.Missing Data in Clinical Studies. Chichester, UK: Whiley; 2007.
citation: Moscovitch DA, Hofmann SG, Suvak MK, In-Albon T. Mediation of changes in anxiety and depression during treatment of social phobia. J Consult Clin Psychol. 2005 Oct;73(5):945-952. doi: 10.1037/0022-006X.73.5.945.
citation: Rief W, Hiller W. A new approach to the assessment of the treatment effects of somatoform disorders. Psychosomatics. 2003 Nov-Dec;44(6):492-8. doi: 10.1176/appi.psy.44.6.492.
citation: Rief W, Rojas G. Stability of somatoform symptoms--implications for classification. Psychosom Med. 2007 Dec;69(9):864-9. doi: 10.1097/PSY.0b013e31815b006e.
citation: Rieffe C, Terwogt MM, Bosch JD, Kneepkens CMF, Douwes AC, Jellesma FC. Interaction between emotions and somatic complaints in children who did or did not seek medical care. Cognition Emotion 21(8):1630-1646, 2007.
citation: Waller E, Scheidt CE. Somatoform disorders as disorders of affect regulation: a study comparing the TAS-20 with non-self-report measures of alexithymia. J Psychosom Res. 2004 Sep;57(3):239-47. doi: 10.1016/S0022-3999(03)00613-5.
citation: Witthoft M, Rist F, Bailer J. Abnormalities in cognitive-emotional information processing in idiopathic environmental intolerance and somatoform disorders. J Behav Ther Exp Psychiatry. 2009 Mar;40(1):70-84. doi: 10.1016/j.jbtep.2008.04.002. Epub 2008 May 23.
citation: Senger K, Rubel JA, Kleinstauber M, Schroder A, Kock K, Lambert MJ, Lutz W, Heider J. Symptom change trajectories in patients with persistent somatic symptoms and their association to long-term treatment outcome. Psychother Res. 2022 Jun;32(5):624-639. doi: 10.1080/10503307.2021.1993376. Epub 2021 Oct 29.
citation: Schwarz J, Rief W, Radkovsky A, Berking M, Kleinstauber M. Negative affect as mediator between emotion regulation and medically unexplained symptoms. J Psychosom Res. 2017 Oct;101:114-121. doi: 10.1016/j.jpsychores.2017.08.010. Epub 2017 Aug 10.
citation: Kleinstauber M, Gottschalk J, Berking M, Rau J, Rief W. Enriching Cognitive Behavior Therapy with Emotion Regulation Training for Patients with Multiple Medically Unexplained Symptoms (ENCERT): Design and implementation of a multicenter, randomized, active-controlled trial. Contemp Clin Trials. 2016 Mar;47:54-63. doi: 10.1016/j.cct.2015.12.003. Epub 2015 Dec 4.