Clinical trial NCT02426788: CBT Plus SMC Compared to SMC for Persistent Physical Symptoms in Secondary Care (PRINCE)
Official title: The PRINCE Secondary Study: Persistent Physical Symptoms Reduction Intervention: a System Change and Evaluation in Secondary Care
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Persistent Physical Symptoms (PPS)
Keywords: medically unexplained
fibromyalgia
postural orthostatic tachycardia syndrome (PoTs)
non-cardiac chest pain
CFS
irritable bowel syndrome (IBS)
functional neurological
chronic pain
hyperventilation
unexplained cough
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: South London and Maudsley NHS Foundation Trust
First posted: 2015-04-27
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Brief Summary: Persistent Physical Symptoms (PPS), also known as medically unexplained symptoms (MUS) is a term used to describe a range of persistent bodily symptoms for which the exact cause is unclear. Between 20 and 40% of patients in primary care, and about 50% in secondary care experience PPS. Not only are PPS common, but the overlap across different patient groups may indicate that these phenomena are transdiagnostic. PPS are associated with profound disability and high health care costs, and if left untreated the prognosis of these patients is poor. There is an accumulating body of evidence demonstrating that cognitive behavioural interventions can reduce levels of symptoms and improve functioning in patients with PPS. A pragmatic randomised controlled trial (RCT) was designed to evaluate the clinical and cost-effectiveness of cognitive behavioural therapy (CBT) + Standard Medical Care (SMC) versus Standard Medical Care alone, in the treatment of patients with PPS. The trial will focus on patients with a variety of symptoms (e.g., non-cardiac chest pain, fibromyalgia), across secondary care clinics (e.g., neurology, cardiology, and rheumatology).

Detailed description: Background and study aims In primary care between 20 and 40% of patients have medically unexplained physical symptoms. The term medically unexplained symptoms (MUS) is commonly used by health care professionals. However a survey of a healthy population and a separate survey of patients with chronic fatigue syndrome (CFS) suggested that the term persistent physical symptoms (PPS) was the preferred term. The term PPS may have its drawbacks, but it will be used in the rest of this document to cover MUS as well as any other terms that may be used in the literature and clinical settings to refer to these symptoms. In secondary care, about 50% of patients have PPS, in many specialties. PPS are associated with profound disability and high health care costs. Around 50% of sufferers have co-morbid anxiety and depression and sleep problems. Left untreated, the prognosis of these patients is poor.

This study is a pragmatic RCT that will evaluate the clinical and cost-effectiveness of cognitive behavioural therapy + standard medical care (CBT+SMC), which involves 8 sessions of CBT, versus standard medical care (SMC) in the treatment of patients with PPS.

Who can participate? Patients with various PPS, such as fibromyalgia, non-cardiac chest pain, irritable bowel syndrome and a range of neurological symptoms e.g., weakness will be recruited. Participants will be recruited from clinics in secondary care (e.g., neurology, cardiology, rheumatology) at various hospitals in London.

What does the study involve? Potential participants will be identified by clinical staff who will refer them to the research team. Patients who give their consent to take part in the study will complete a number of questionnaires asking about their symptoms and use of health care services, and about their thoughts, feelings, and beliefs related to their PPS (i.e., baseline). This will take approximately 1.5 hours. After this research assessment, half of participants will be randomly assigned to the treatment arm (CBT+SMC), or to the control (SMC) arm. Participants in the treatment arm will receive 8 individual sessions of CBT (weekly or fortnightly sessions). The therapy aims to help the patient develop an understanding of the relationship between cognitive, physiological and behavioural aspects of their problem; to understand factors that may be maintaining the problem and to learn how to modify their behavioural and cognitive responses in order to improve their quality of life. Participants in the SMC group will receive usual medical care within the clinic.

Participants in both arms will also be asked to complete questionnaires at 9, 20, 40, and 52 weeks after randomisation. The assessment will be independent of the health care professionals delivering care.

What are the possible benefits and risks of participating? By taking part in the study patients may get helpful information about their condition. If assigned to the CBT+SMC arm, patients will receive 8 sessions of CBT focused on helping them manage their symptoms, which may improve their symptoms and increase their psychosocial functioning. It is unclear whether CBT for patients with PPS is effective; this trial will assess whether there are benefits to receiving it. Patients may benefit from being followed up closely and completing measures. It is not expected that participation in the study is associated with risks. The therapists involved in the trial are highly qualified specialists with extensive experience in treating patients with PPS. The trial team also includes a psychiatrist who will further ensure patient safety in complex cases. Participants will be free to take a break at any point during the meetings and are free to withdraw from the study at any point. Participants will also be informed that they can raise any concerns they may have with the research team and will be provided with the Patient Advice \& Liaison Service contact information.

Where is the study run from? The study has been set up by the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King's College London and the South London and Maudsley National Health Service (NHS) Foundation Trust, and will be conducted at several hospitals in London/Greater London, including Guy's and St Thomas' Hospitals, King's College Hospital, Princess Royal University Hospital, Royal Free Hospital, University Hospital Lewisham and Queen Elizabeth Hospital.

When is the study starting and how long is it expected to run for? The study has started in July 2015 and the end date for the project is March 2019.

Who is funding the study? The study is funded by the Guy's and St. Thomas' Charity.

Who is the main contact? Prof Trudie Chalder trudie.chalder@kcl.ac.uk

Eligibility criteria: * Adults (18 - 70 yrs)
* Patients with PPS from broad patient populations (e.g., fibromyalgia, non-cardiac chest pain, postural orthostatic tachycardia syndrome, neurological symptoms);
* Significant functional impairment/moderately severe disability - as indicated by the Work and Social Adjustment Scale (WSAS) score (i.e., a minimum score of 10);
* Ability to complete diaries and questionnaires in English;
* Willingness to complete all trial visits;
* Ability to give written informed consent.

Exclusion Criteria:

* Active psychosis;
* Factitious disorder;
* Headaches as the only PPS;
* Non-epileptic seizures
* Current alcohol dependence or drug addiction as assessed by the clinician;
* Current benzodiazepine use exceeding the equivalent of 10mg diazepam/day;
* The patient is currently receiving CBT/CBT based approach psychotherapy, or has received CBT/CBT based approach psychotherapy in the past year, for their PPS;
* The patient is thought to be at imminent risk of self-harm;
* Patient is taking part in PRINCE Primary trial.

Primary outcomes:
measure: Work and social adjustment scale
timeFrame: 52 weeks post randomisation
Secondary outcomes:
measure: Persistent Physical Symptom Questionnaire
timeFrame: 52 weeks post randomisation
measure: Patient Health Questionnaire-15 (PHQ-15)
timeFrame: 52 weeks post randomisation
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: 52 weeks post randomisation
measure: Generalized Anxiety Disorder-7 (GAD-7)
timeFrame: 52 weeks post randomisation
measure: Clinical Global Impression (CGI)
timeFrame: 52 weeks post randomisation
measure: Client Service Receipt Inventory (CSRI)
timeFrame: 52 weeks post randomisation
measure: EuroQol-5D (EQ-5D)
timeFrame: 52 weeks post randomisation
measure: Cognitive Behavioural Responses Questionnaire
timeFrame: 52 weeks post randomisation
measure: Acceptance scale
timeFrame: 52 weeks post randomisation
Other outcomes:
measure: PSYCHLOPS
timeFrame: 52 weeks post randomisation
Locations:
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Queen Elizabeth Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: St Thomas' Hospital
city: London
country: United Kingdom
facility: University Hospital Lewisham
city: Orpington
country: United Kingdom
facility: Princess Royal University Hospital
Study officials:
affiliation: King's College London
name: Trudie Chalder, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chalder T, Patel M, James K, Hotopf M, Frank P, Watts K, McCrone P, David A, Ashworth M, Husain M, Garrood T, Moss-Morris R, Landau S. Persistent physical symptoms reduction intervention: a system change and evaluation in secondary care (PRINCE secondary) - a CBT-based transdiagnostic approach: study protocol for a randomised controlled trial. BMC Psychiatry. 2019 Oct 22;19(1):307. doi: 10.1186/s12888-019-2297-y.