Persistent Physical Symptoms (PPS)PRINCENCT02426788
CBT Plus SMC Compared to SMC for Persistent Physical Symptoms in Secondary Care (PRINCE)
A study testing Cognitive behavioural therapy (CBT) in people with Persistent Physical Symptoms (PPS), run by King's College London at 7 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Persistent Physical Symptoms (PPS)
- What is being tested?
- Cognitive behavioural therapy (CBT)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 324 participants
- Where
- 7 sitesUnited Kingdom
- Study dates
- Jul 2015to Jan 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United Kingdom7 sites
Guy's Hospital
London
King's College Hospital
London
Queen Elizabeth Hospital
London
Royal Free Hospital
London
St Thomas' Hospital
London
University Hospital Lewisham
London
Princess Royal University Hospital
Orpington
About this study
Official title: The PRINCE Secondary Study: Persistent Physical Symptoms Reduction Intervention: a System Change and Evaluation in Secondary Care
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).
Read the 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
- Conditions
- Persistent Physical Symptoms (PPS)
- Being tested
- Cognitive behavioural therapy (CBT)
- 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
- Medical subject headings
- Fibromyalgia, Postural Orthostatic Tachycardia Syndrome, Irritable Bowel Syndrome, Chronic Pain, Hyperventilation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive behavioural therapy (CBT)Behavioural
Behavioral: Cognitive behavioural therapy (CBT) The CBT intervention used in the trial has been adapted for people with PPS and it is based on a model of understanding PPS (Deary et al 2007). 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 quality of life. The approach is transdiagnostic in that it targets processes and underlying mechanisms that affect disorders similarly, rather than focusing on how they are diagnostically different. The approach is personalised during therapy following a detailed assessment.
| Study group | Role | What they receive |
|---|---|---|
| CBT+SMC | Experimental | Cognitive behavioural therapy + Standard Medical Care (cognitive-behavioural therapy+SMC):
8 hour-long manual-based CBT sessions with a therapist, weekly or fortnightly. Receives: Behavioral: Cognitive behavioural therapy (CBT) |
| Standard Medical Care (SMC) | No intervention | Participants assigned to the SMC group (i.e., control group) will receive all the treatment and support they would otherwise receive outside of a research trial. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Work and social adjustment scale
Measures impairment in functioning
Measured: 52 weeks post randomisation
Secondary outcomes (9)
Persistent Physical Symptom Questionnaire
Measures severity, distress, interference and problematic nature of PPS
Measured: 52 weeks post randomisation
Patient Health Questionnaire-15 (PHQ-15)
Measures physical symptoms severity
Measured: 52 weeks post randomisation
Patient Health Questionnaire-9 (PHQ-9)
Measures mood
Measured: 52 weeks post randomisation
Generalized Anxiety Disorder-7 (GAD-7)
Measures generalised anxiety
Measured: 52 weeks post randomisation
Clinical Global Impression (CGI)
Measures patient's perception of their general health improvement
Measured: 52 weeks post randomisation
Client Service Receipt Inventory (CSRI)
Measures health care service receipt, direct and indirect costs of illness, and cost-effectiveness of interventions
Measured: 52 weeks post randomisation
EuroQol-5D (EQ-5D)
Measures health outcome
Measured: 52 weeks post randomisation
Cognitive Behavioural Responses Questionnaire
Measures beliefs and behaviours
Measured: 52 weeks post randomisation
Acceptance scale
assesses degree of acceptance of difficult symptoms
Measured: 52 weeks post randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2015 (estimated)
- Study startJul 2015
- Primary completionJan 2019
- Study completionJan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Persistent Physical Symptoms (PPS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 324 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- South London and Maudsley NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Trudie Chalder, PhD, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02426788
- Sponsor's protocol ID
- STR130202 (Secondary)
- Acronym
- PRINCE
- Status last verified
- Aug 2018
- First submitted
- 22 Apr 2015
- Last updated
- 9 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 31640632
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The PRINCE Secondary Study: Persistent Physical Symptoms Reduction Intervention: a System Change and Evaluation in Secondary Care
- ClinicalTrials.gov ID
- NCT02426788
- Acronym / sponsor ID
- PRINCE / STR130202 (Secondary)
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 324 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- South London and Maudsley NHS Foundation Trust
- Study start
- Jul 2015
- Primary completion
- Jan 2019 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 27 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CBT+SMC | Experimental | Behavioral: Cognitive behavioural therapy (CBT)Cognitive behavioural therapy + Standard Medical Care (cognitive-behavioural therapy+SMC): 8 hour-long manual-based CBT sessions with a therapist, weekly or fortnightly. |
| Standard Medical Care (SMC) | No intervention | –Participants assigned to the SMC group (i.e., control group) will receive all the treatment and support they would otherwise receive outside of a research trial. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (9 listed)
- Active psychosis;
- Factitious disorder;
- Headaches as the only PPS;
- Non-epileptic seizures
- Current alcohol dependence or drug addiction as assessed by the clinician;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive behavioural therapy (CBT)Behavioral: Cognitive behavioural therapy (CBT) The CBT intervention used in the trial has been adapted for people with PPS and it is based on a model of understanding PPS (Deary et al 2007). 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 quality of life. The approach is transdiagnostic in that it targets processes and underlying mechanisms that affect disorders similarly, rather than focusing on how they are diagnostically different. The approach is personalised during therapy following a detailed assessment. | Behavioural | CBT+SMC |
Primary outcome
Work and social adjustment scale
Time frame: 52 weeks post randomisation
Measures impairment in functioning
9 secondary outcomes
Persistent Physical Symptom Questionnaire
Time frame: 52 weeks post randomisation
Patient Health Questionnaire-15 (PHQ-15)
Time frame: 52 weeks post randomisation
Patient Health Questionnaire-9 (PHQ-9)
Time frame: 52 weeks post randomisation
Generalized Anxiety Disorder-7 (GAD-7)
Time frame: 52 weeks post randomisation
Clinical Global Impression (CGI)
Time frame: 52 weeks post randomisation
Client Service Receipt Inventory (CSRI)
Time frame: 52 weeks post randomisation
EuroQol-5D (EQ-5D)
Time frame: 52 weeks post randomisation
Cognitive Behavioural Responses Questionnaire
Time frame: 52 weeks post randomisation
Acceptance scale
Time frame: 52 weeks post randomisation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2019.
- Derived from this study: PubMed 31640632Chalder 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.
- Individual participant dataSharing planned: No
Related trials for Persistent Physical Symptoms (PPS)
Active, not recruitingObservational study
The Pilot of the Turku Outpatient Clinic for Functional and Fatigue Disorders
Persistent Physical Symptoms (PPS), Functional Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Trudie Chalder, PhD principal investigator
King's College London
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive behavioural therapy (CBT) in people with Persistent Physical Symptoms (PPS), run by King's College London at 7 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Work and social adjustment scale (time frame: 52 weeks post randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02426788, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2019.