Efficacy of Patient Education and Duloxetine, Alone or in Combination, for Patients With Multisystem Functional Somatic Disorder
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 424
- 试验地点
- 1
- 主要终点
- Mean difference between groups in Short-Form Health Survey (SF-36) aggregate score
研究概览
简要总结
The goal of this clinical trial is to test if patient education or duloxetine can be used to treat multisystem functional somatic disorder (FSD). The main questions it aims to answer are:
- Does duloxetine work better than placebo in the treatment of FSD?
- Does patient education work better than usual treatment for FSD?
- Does the combination of patient education and duloxetine work better than using only one of these treatments?
Participants are patients with FSD. They will receive one of six different treatment combinations:
- Patient education alone (three individual consultations with a doctor and one group session)
- Treatment as usual (receiving the diagnosis and a short presentation of what FSD is)
- Duloxetine
- Active placebo (a treatment that looks like duloxetine and has similar side effects, but no known effect on FSD)
- Patient education and duloxetine
- Patient education and active placebo
Researchers will compare the groups receiving patient education with those receiving only treatment as usual to see if patient education is a better treatment than just receiving a diagnosis and short explanation. Furthermore, researchers will compare the groups receiving duloxetine to those receiving placebo to see if duloxetine works better than placebo. Finally, researchers will compare the groups receiving both patient education and duloxetine to those receiving only one of these treatments to see if the combination works better than the treatments given alone.
The researchers will also collect samples of blood and stool in a biobank to be used in future research.
详细描述
Background Functional somatic disorders (FSD) are characterized by specific patterns of persistent physical symptoms with a complex etiology involving a multiform interplay between physiological, psychological, and socio-cultural factors. Patients with FSD are prevalent in all medical settings and receive diagnoses such as fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and other functional somatic syndromes (FSS) depending on which medical specialty they consult. Multisystem FSD describes a severely affected subgroup of patients who suffer from symptoms from multiple organ systems. The diagnosis can be operationalized by the criteria for the unifying research diagnosis bodily distress syndrome (BDS).
Multisystem FSD affects 1.3-2.2% of the general population. The condition inflicts suffering and is associated with a substantial socioeconomic impact, involving costly diagnostic examinations and procedures, sick leaves, and long-term disability.
Evidence on treatment options for multisystem FSD is emerging but not yet sufficient. A number of clinical trials investigating non-pharmacological interventions are available and clinical guidelines in some FSS, e.g. fibromyalgia and chronic primary pain, highlight the importance of patient education (PE). PE may support the effect of other treatments by empowering and engaging patients in managing their condition. As a stand-alone treatment, the effect of PE has only sparsely been investigated, yet a PE program targeting multisystem FSD has been tested in an uncontrolled pilot study with promising results.
Pharmacotherapy in FSS includes centrally acting drugs, especially antidepressants. In multisystem FSD, evidence exists for treatment with low-dose tricyclic antidepressants (TCA). Unfortunately, TCAs given in higher, antidepressive doses significantly reduces tolerability and thereby treatment potential for comorbid depression or anxiety which are common in multisystem FSD. Duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI), offers effect sizes similar to low-dose TCA in FSS with a more favorable adverse event profile. Evidence furthermore suggests an effect on cognitive functioning. In addition to reducing symptoms in multisystem FSD, duloxetine could improve cognitive functioning and, if relevant, treat comorbid anxiety and depression.
From a clinical perspective, a synergic effect between a PE program and pharmacological treatment could be hypothesized. On one hand, PE may improve the effect of pharmacological treatment by balancing treatment expectations and enhancing treatment adherence. Conversely, pharmacological treatment may indirectly enhance the effect of PE by improving cognitive functioning and thereby improving the patients' ability to receive and implement relevant educational elements.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Randomization for both the open-label parent trial and the nested blinded study drug trial will be carried out using REDCap. The randomization code will be generated by an independent employee through REDCap. Coded (numbered) packs of study drug and active placebo will be produced according to the randomization schedule. Patients, clinicians, investigators, and all other staff involved in the conduct or data analysis of the nested trial will be masked to study drug treatment allocation for the duration of the study and throughout all data analysis. Patients and clinicians will be asked to guess allocated treatment (duloxetine or active placebo) and indicate reason at endpoints to evaluate blinding efficacy.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Patient Education
The patient education program consists of three individual sessions (consultations with the participant's doctor, one to one and a half hour duration each) and one group session (three hours in groups of up to 16 participants). The program focuses on providing patients with a positive and evidence-based understanding of their illness by providing an individualized bio-psycho-social explanation of multisystem functional somatic disorder.
干预措施: Patient Education (Behavioral)
Enhanced Usual Care
Inclusion consultation and final visit at end of treatment (week 12) are the only contacts provided to participants randomized to receive enhanced usual care.
干预措施: Enhanced usual care (Behavioral)
Duloxetine and Enhanced Usual Care
Duloxetine will be given as capsules orally once daily. Participants will commence with 2 weeks of 30 mg duloxetine and then increase the dose to 60 mg duloxetine (two capsules). If participants are unable to increase in dose due to adverse events, but still tolerate the initial dose of 30 mg duloxetine, this dose is kept for the remaining part of the trial. Treatment will continue for 8 weeks on highest dosis until primary endpoint (end of treatment). The dose is then reduced to 30 mg duloxetine for 1 week after which the study drug is discontinued.
In addition, participants will recieve enhanced usual care as described above.
干预措施: Duloxetine (Drug)
Duloxetine and Enhanced Usual Care
Duloxetine will be given as capsules orally once daily. Participants will commence with 2 weeks of 30 mg duloxetine and then increase the dose to 60 mg duloxetine (two capsules). If participants are unable to increase in dose due to adverse events, but still tolerate the initial dose of 30 mg duloxetine, this dose is kept for the remaining part of the trial. Treatment will continue for 8 weeks on highest dosis until primary endpoint (end of treatment). The dose is then reduced to 30 mg duloxetine for 1 week after which the study drug is discontinued.
In addition, participants will recieve enhanced usual care as described above.
干预措施: Enhanced usual care (Behavioral)
Placebo and Enhanced Usual Care
Participants will recieve the active placebo benztropine mesylate 0,5 mg. In order to best mimic the dosage increase of the duloxetine treatment program a passive placebo RAP will be added for the 8 weeks of high dosage treatment. Benztropine mesylate and passive placebo will be given as capsules orally, and will be re-encapsulated by the hospital pharmacy to assure identical appearance to the duloxetine capsules. Participants will commence with 2 weeks of 0.5 mg benztropine mesylate (one capsule) and continue with 0.5 mg benztropine mesylate and passive placebo RAP (two capsules) for 8 weeks. This will be end of treatment. Participants will then be asked to reduce to one capsule (0.5 mg benztropine mesylate) for 1 week after which the study drug is discontinued.
In addition, participants will recieve enhanced usual care as decribed above.
干预措施: Benztropine Mesylate 0.5 MG and passive placebo RAP (Drug)
Placebo and Enhanced Usual Care
Participants will recieve the active placebo benztropine mesylate 0,5 mg. In order to best mimic the dosage increase of the duloxetine treatment program a passive placebo RAP will be added for the 8 weeks of high dosage treatment. Benztropine mesylate and passive placebo will be given as capsules orally, and will be re-encapsulated by the hospital pharmacy to assure identical appearance to the duloxetine capsules. Participants will commence with 2 weeks of 0.5 mg benztropine mesylate (one capsule) and continue with 0.5 mg benztropine mesylate and passive placebo RAP (two capsules) for 8 weeks. This will be end of treatment. Participants will then be asked to reduce to one capsule (0.5 mg benztropine mesylate) for 1 week after which the study drug is discontinued.
In addition, participants will recieve enhanced usual care as decribed above.
干预措施: Enhanced usual care (Behavioral)
Patient Education and Duloxetine
Participants in this arm will recieve patient education as described above. In addition, participants will recieve duloxetine as described above.
干预措施: Patient Education (Behavioral)
Patient Education and Duloxetine
Participants in this arm will recieve patient education as described above. In addition, participants will recieve duloxetine as described above.
干预措施: Duloxetine (Drug)
Patient Education and Placebo
Participants in this arm will recieve patient education as described above. In addition, participants will recieve the placebo treatment as described above.
干预措施: Patient Education (Behavioral)
Patient Education and Placebo
Participants in this arm will recieve patient education as described above. In addition, participants will recieve the placebo treatment as described above.
干预措施: Benztropine Mesylate 0.5 MG and passive placebo RAP (Drug)
结局指标
主要结局
Mean difference between groups in Short-Form Health Survey (SF-36) aggregate score
时间窗: T0 (baseline, before assessment), T1(after inclusion, before randomization), T2 (week 6, mid-treatment), T3 (primary endpoint, week 12), T4 (3-month after end of treatment), T5 (1-year follow-up), T6 (2-year follow-up)
Patient-rated health-related quality of life is measured by an aggregate score of the SF-36 subscales "physical functioning", "bodily pain" and "vitality" at endpoint (week 12). Minimum score is 15 and maximum score is 62 with lower scores indicating worse health related quality of life. Primary outcome will be measured as the change from baseline to primary endpoint (12 weeks), but data will be collected on several timepoints to describe the development on the score
Mean difference between groups in Clinical Global Improvement Scale (CGI) score
时间窗: T3 (primary endpoint, 12 weeks), T4 (3-month follow-up), T5 (1-year follow-up), T6 (2-year follow-up)
Patient-rated overall health improvement measured by the 5-point CGI. General health is rated as "much worse", "worse", "unchanged", "better" or "much better" in response to the question: "How do you consider your health status now compared with when you first came to the clinic?".
次要结局
- Mean difference between groups in the Bodily Distress Syndrome (BDS) check-list score(T0 (baseline, before assessment), T1(before randomization), T3 (primary endpoint, 12 weeks), T4 (3-month follow-up), T5 (1-year follow-up), T6 (2-year follow-up))
- Mean difference between groups in Numeric Rating Scale (NRS) on symptom intensity and symptom interference(T0 (baseline, before assessment), T1(before randomization), T2 (week 6, mid-treatment), T3 (primary endpoint, 12 weeks), T4 (3-month follow-up), T5 (1-year follow-up), T6 (2-year follow-up))
- Mean difference between groups in Behavioural Responses to Illness Questionnaire (BRIQ)(T0 (baseline, before assessment), T1(before randomization), T2 (week 6, mid-treatment), T3 (primary endpoint, 12 weeks), T4 (3-month follow-up), T5 (1-year follow-up), T6 (2-year follow-up))
- Mean difference between groups in the Symptom Checklist (SCL-92) score on subscales somatic symptoms (SCL-som), anxiety and depression (SCL-anx 4, SCL-depr 6)(T0 (baseline, before assessment), T1(before randomization), T2 (week 6, mid-treatment), T3 (primary endpoint, 12 weeks), T4 (3-month follow-up), T5 (1-year follow-up), T6 (2-year follow-up))
- Mean difference between groups in Whiteley-6-R score(T0 (baseline, before assessment), T1(before randomization), T2 (week 6, mid-treatment), T3 (primary endpoint, 12 weeks), T4 (3-month follow-up), T5 (1-year follow-up), T6 (2-year follow-up))
- Mean difference between groups in Cognitive Failures Questionnaire (CFQ) score(T1(before randomization), T2 (week 6, mid-treatment), T3 (primary endpoint, 12 weeks))
- Mean difference between groups in Patients' Endorsement of a Biopsychosocial Model of Pain/Persistent Somatic Symptoms (PEB) score(T1(before randomization), T2 (week 6, mid-treatment), T3 (primary endpoint, 12 weeks), T4 (3-month follow-up), T5 (1-year follow-up), T6 (2-year follow-up))
- Mean difference between groups in Numeric Rating Scale (NRS) on pain intensity(T0 (baseline, before assessment), T1(before randomization), T2 (week 6, mid-treatment), T3 (primary endpoint, 12 weeks), T4 (3-month follow-up), T5 (1-year follow-up), T6 (2-year follow-up))
- Mean difference between groups in Brief-Illness Perception Questionnaire (b-IPQ)(T0 (baseline, before assessment), T1(before randomization), T2 (week 6, mid-treatment), T3 (primary endpoint, 12 weeks), T4 (3-month follow-up), T5 (1-year follow-up), T6 (2-year follow-up))
- Mean difference between groups in clinician-rated Clinical Global Improvement Scale (CGI) score(T3 (primary endpoint, 12 weeks))
- Mean difference between groups in diagnosis based on a clinical diagnostic reassessment(T3 (primary endpoint, 12 weeks))