Cerebral PalsyPhase 3POPPIESNCT01437644
The Post-Operative Pain in Cerebral Palsy (POPPIES) Trial
A Phase 3 study testing botulinum toxin intramuscular injection in people with Cerebral Palsy and Post-operative Pain, run by Guy's and St Thomas' NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Cerebral palsy is common. It affects approximately 3 per 1000 children. Hip displacement due to muscle tightness (spasticity) occurs in up to half of the more severely affected children, and many of these children require major (bony) hip surgery. Read more about this study
- Who is it for?
- Ages 2 to 15 years
- Conditions the study is for
- Cerebral Palsy, Post-operative Pain
- What is being tested?
- botulinum toxin intramuscular injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2011to Jan 2015
- Phase
- Phase 3
- 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 2 to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- The child has displaced hips requiring bony orthopaedic surgery (osteotomy) due to cerebral palsy (appendix 2).
- The child is between the ages of 2 and 15 years (inclusive).
- The child has a GMFCS level of IV or V
- The child has a diagnosis of hypertonic cerebral palsy (or a diagnosis consistent with this nomenclature)
- The child does not communicate verbally
- Informed consent to participate has been given by parent/carer.
Who cannot join
- The child is younger than 2 years or older than 15 years
- The child has an acute and current systemic infection or illness
- The child has had botulinum toxin injections within the past 4 months
- The child has had a previous reaction to botulinum toxin
- The child has received or is likely to receive, at the time of trial drug or placebo administration, medications which might interact with botulinum toxin (this does not apply to any drugs at present)
- Insufficient understanding of the trial by the parent or carer, in the investigator's opinion.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Guy's and St Thomas' NHS Foundation Trust
London, London, SE1 7EH
About this study
Official title: Post-operative Pain in Children With Cerebral Palsy Following Major Hip Surgery: a Double Blind Randomised Placebo Controlled Trial of Pre-operative Botulinum Toxin Type A
Cerebral palsy is common. It affects approximately 3 per 1000 children. Hip displacement due to muscle tightness (spasticity) occurs in up to half of the more severely affected children, and many of these children require major (bony) hip surgery. After bony hip surgery the management of pain is very difficult, as spasticity tends to increase and causes painful spasms which are difficult to control. Botulinum Toxin injections are known to reduce spasticity and therefore should also reduce pain. These injections take at least a week to work, but the effects can last for months. Botulinum Toxin is already an established treatment for chronic hip pain prior to surgery. The investigators aim to find out whether Botulinum Toxin injections can reduce post-operative pain. The identification of the level of pain can be challenging because most of these children are unable to communicate verbally. The investigators are therefore using a validated pain scoring tool that was designed especially for such children. This study will be the first to describe fully the pain experience of children with cerebral palsy undergoing this type of major surgery. The investigators will compare Botulinum Toxin injections with placebo (non-active) injections. There is a high emotional and financial burden on the families of these children. Families describe high levels of emotional distress around the time of surgery, particularly when their child is in pain. Difficulty with pain control post operatively may delay discharge from hospital and parental return to work. It causes disrupted sleep for the child and family and may delay the child's return to school. The results of this study will be shared with professionals and families at international conferences and in scientific and popular (patient-based) publications. This study cannot be undertaken in adults with cerebral palsy as they only rarely undergo this sort of surgery.
Read the detailed description
Botulinum toxin injected intramuscularly is beneficial in the management of spasticity and as a treatment for chronic hip pain in children with cerebral palsy. Botulinum injections also seem to be useful in reducing spasticity in the acute post operative period; the benefits of botulinum toxin have been described in one study for post-operative pain following minor hip surgery. After major (bony) hip surgery these children experience significantly more pain, which also seems to be exacerbated by spasticity. Botulinum toxin may therefore reduce pain following major hip surgery. Research is required to assess its value in this setting. This cannot be studied in adults as they rarely undergo such surgery.
Cerebral palsy (CP) is the commonest cause of physical disability in childhood, it affects up to 3 children per 1000 throughout Europe (1;2). The Gross Motor Function Classification System (GMFCS) was designed for children and describes their level of motor skill (3). Over 25% of children with CP probably fall in the more severely affected groups - GMFCS levels IV and V. These children are not independently ambulant and are more likely to have cognitive and communication difficulties. They are at high risk of developing hip displacement (ie the hip gradually comes out of its socket) (4-10). Previous studies suggest that up to half of these hips are painful and it is well-established that hip displacement is painful for some children (14-18). Prevention of painful hip displacement has been advocated through screening programmes and timely surgical intervention (11-13). Some children need bony reconstructive surgery. Long term follow up studies have demonstrated that this maintains the position of the femoral head in the acetabulum over time, reducing the likelihood of a painful hip due to dislocation (9;10).
The management of pain in the severely neurologically impaired child undergoing hip (or any other) surgery is challenging and various strategies have been employed, including the use of post-operative epidurals. In a child with spasticity abnormally high post-operative muscle tone may be a cause painful muscle spasms. These involuntary and sustained muscle contractions are thought to contribute significantly to pain in children with cerebral palsy and a hip problem. There are a number of treatments available for muscle spasm in cerebral palsy; all are systemic except botulinum toxin which targets individual muscles by means of intramuscular injection. Botulinum toxin type A (BTXA) injection is a well established, clinically effective and safe treatment for muscle spasticity in CP (2;19;20). Research suggests it may have a beneficial effect in reducing pain due to spasticity (18). Graham and co-workers established that BTXA was safe in the perioperative period for children with cerebral palsy undergoing soft tissue surgery for a hip problem. Lundy and Fairhurst demonstrated BTXA is safe and effective in children with severe cerebral palsy, GMFCS IV\&V when doses are given in line with the European Consensus guidelines. (24) Work on pain in children with CP suggests that anxiety and unrelieved pain may stimulate the autonomic nervous system in such a way that these children may actually have an amplified pain response when undergoing surgical procedures. Actions such as stretching muscles in a cast or for rehabilitation exercises may exacerbate spasms and therefore increase pain (8;17;21).
Describing pain in children with cognitive impairment however is challenging. Studies have focused on the report of pain symptoms, duration, intensity and analgesia requirements. Hunt et al provided a validated pain profile questionnaire which objectively measures pain in the more severely neurologically affected group of children with communication difficulties (22). The investigators have gained experience using this Paediatric Pain Profile to describe levels of pain in this group of children. It is a validated and user friendly system, already in place at this institution.
- Conditions
- Cerebral Palsy, Post-operative Pain
- Being tested
- botulinum toxin intramuscular injection
- Keywords
- Cerebral Palsy, Hip displacement, Hip surgery, Post-operative pain, Botulinum Toxin
- Medical subject headings
- Cerebral Palsy, Pain, Postoperative, Hip Dislocation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
botulinum toxin intramuscular injectionDrug
Also called Botox, Allergan.
A single dose of active drug or placebo will be administered immediately prior to surgery.
The injections will be given to the anaesthetised child before the surgical procedure begins. The surgeon will perform the injections at three muscle groups around each hip: the adductors, hamstrings and iliopsoas muscles. Two units per kilogram will be given at each site. The maximum dose will be 12 units per kilogram or 500 units in total (whichever is the lesser), divided equally between six or three sites. Each active drug vial will contain 100 iu of the Botox preparation. The volume injected will be dependent on the weight of the child. Injections of normal saline will be administered in those children randomised to the placebo.
| Study group | Role | What they receive |
|---|---|---|
| Botulinum Toxin TypeA | Active comparator | A single dose of active drug or placebo will be administered immediately prior to surgery.
The injections will be given to the anaesthetised child before the surgical procedure begins. The surgeon will perform the injections at three muscle groups around each hip: the adductors, hamstrings and iliopsoas muscles. Two units per kilogram will be given at each site. The maximum dose will be 12 units per kilogram or 500 units in total (whichever is the lesser), divided equally between six or three sites. A total of 2 ml of isotonic saline will be used to dissolve the contents of the trial vial of Botox. Each active drug vial will contain 100 iu of the Botox preparation. The volume injected will be dependent on the weight of the child. Injections of normal saline will be administered in those children randomised to the placebo arm of the study. Receives: Drug: botulinum toxin intramuscular injection |
| Saline | Placebo comparator | The injections will be given to the anaesthetised child before the surgical procedure begins. The surgeon will perform the injections at three muscle groups around each hip: the adductors, hamstrings and iliopsoas muscles. Injections of normal saline will be administered in those children randomised to the placebo arm of the study. The volume of normal saline injected will be equal to the volume of normal saline that would have been used if the child had been randomised to botulinum toxin. The injector will be blinded, as the solution is drawn up by unblinded nurses. Receives: Drug: botulinum toxin intramuscular injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Paediatric Pain Profile
The primary endpoint is the change in pain score during the six weeks following the operation. Pain will be measured using a validated questionnaire, the Paediatric Pain Profile. This scores pain by rating twenty different items of observed behaviour on an ordinal scale of 0 to 3 with a composite score of 0 to 60. It has been validated in children with severe cerebral palsy.
Measured: 6 weeks post-op
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2011 (estimated)
- Study startOct 2011
- Primary completionSep 2014
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral PalsyStudies of the same condition, open and under way.
- More trials run by Guy's and St Thomas' NHS Foundation TrustThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Guy's and St Thomas' NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fabian Norman-Taylor, Guy's and St Thomas' NHS Foundation Trust
- Investigators
- Rebecca Newton, Study director, King's Health Partners Clinical Trials Office
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01437644
- Sponsor's protocol ID
- 2010-023240-33
- Other IDs
- PB-PG-1208-18132, 2010-023240-33, 11/WA/0010
- Acronym
- POPPIES
- Status last verified
- Apr 2015
- First submitted
- 19 Sep 2011
- Last updated
- 1 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Post-operative Pain in Children With Cerebral Palsy Following Major Hip Surgery: a Double Blind Randomised Placebo Controlled Trial of Pre-operative Botulinum Toxin Type A
- ClinicalTrials.gov ID
- NCT01437644
- Acronym / sponsor ID
- POPPIES / 2010-023240-33
- Conditions
- Cerebral Palsy, Post-operative Pain
- Keywords
- Cerebral Palsy, Hip displacement, Hip surgery, Post-operative pain, Botulinum Toxin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Guy's and St Thomas' NHS Foundation TrustUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Sep 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 21 Sep 2011 (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.
Cerebral palsy is common. It affects approximately 3 per 1000 children. Hip displacement due to muscle tightness (spasticity) occurs in up to half of the more severely affected children, and many of these children require major (bony) hip surgery. After bony hip surgery the management of pain is very difficult, as spasticity tends to increase and causes painful spasms which are difficult to control. Botulinum Toxin injections are known to reduce spasticity and therefore should also reduce pain. These injections take at least a week to work, but the effects can last for months. Botulinum Toxin is already an established treatment for chronic hip pain prior to surgery. The investigators aim to find out whether Botulinum Toxin injections can reduce post-operative pain. The identification of the level of pain can be challenging because most of these children are unable to communicate verbally. The investigators are therefore using a validated pain scoring tool that was designed especially for such children. This study will be the first to describe fully the pain experience of children with cerebral palsy undergoing this type of major surgery. The investigators will compare Botulinum Toxin injections with placebo (non-active) injections. There is a high emotional and financial burden on the families of these children. Families describe high levels of emotional distress around the time of surgery, particularly when their child is in pain. Difficulty with pain control post operatively may delay discharge from hospital and parental return to work. It causes disrupted sleep for the child and family and may delay the child's return to school. The results of this study will be shared with professionals and families at international conferences and in scientific and popular (patient-based) publications. This study cannot be undertaken in adults with cerebral palsy as they only rarely undergo this sort of surgery.
Detailed description
Botulinum toxin injected intramuscularly is beneficial in the management of spasticity and as a treatment for chronic hip pain in children with cerebral palsy. Botulinum injections also seem to be useful in reducing spasticity in the acute post operative period; the benefits of botulinum toxin have been described in one study for post-operative pain following minor hip surgery. After major (bony) hip surgery these children experience significantly more pain, which also seems to be exacerbated by spasticity. Botulinum toxin may therefore reduce pain following major hip surgery. Research is required to assess its value in this setting. This cannot be studied in adults as they rarely undergo such surgery.
Cerebral palsy (CP) is the commonest cause of physical disability in childhood, it affects up to 3 children per 1000 throughout Europe (1;2). The Gross Motor Function Classification System (GMFCS) was designed for children and describes their level of motor skill (3). Over 25% of children with CP probably fall in the more severely affected groups - GMFCS levels IV and V. These children are not independently ambulant and are more likely to have cognitive and communication difficulties. They are at high risk of developing hip displacement (ie the hip gradually comes out of its socket) (4-10). Previous studies suggest that up to half of these hips are painful and it is well-established that hip displacement is painful for some children (14-18). Prevention of painful hip displacement has been advocated through screening programmes and timely surgical intervention (11-13). Some children need bony reconstructive surgery. Long term follow up studies have demonstrated that this maintains the position of the femoral head in the acetabulum over time, reducing the likelihood of a painful hip due to dislocation (9;10).
The management of pain in the severely neurologically impaired child undergoing hip (or any other) surgery is challenging and various strategies have been employed, including the use of post-operative epidurals. In a child with spasticity abnormally high post-operative muscle tone may be a cause painful muscle spasms. These involuntary and sustained muscle contractions are thought to contribute significantly to pain in children with cerebral palsy and a hip problem. There are a number of treatments available for muscle spasm in cerebral palsy; all are systemic except botulinum toxin which targets individual muscles by means of intramuscular injection. Botulinum toxin type A (BTXA) injection is a well established, clinically effective and safe treatment for muscle spasticity in CP (2;19;20). Research suggests it may have a beneficial effect in reducing pain due to spasticity (18). Graham and co-workers established that BTXA was safe in the perioperative period for children with cerebral palsy undergoing soft tissue surgery for a hip problem. Lundy and Fairhurst demonstrated BTXA is safe and effective in children with severe cerebral palsy, GMFCS IV\&V when doses are given in line with the European Consensus guidelines. (24) Work on pain in children with CP suggests that anxiety and unrelieved pain may stimulate the autonomic nervous system in such a way that these children may actually have an amplified pain response when undergoing surgical procedures. Actions such as stretching muscles in a cast or for rehabilitation exercises may exacerbate spasms and therefore increase pain (8;17;21).
Describing pain in children with cognitive impairment however is challenging. Studies have focused on the report of pain symptoms, duration, intensity and analgesia requirements. Hunt et al provided a validated pain profile questionnaire which objectively measures pain in the more severely neurologically affected group of children with communication difficulties (22). The investigators have gained experience using this Paediatric Pain Profile to describe levels of pain in this group of children. It is a validated and user friendly system, already in place at this institution.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Botulinum Toxin TypeA | Active comparator | Drug: botulinum toxin intramuscular injectionA single dose of active drug or placebo will be administered immediately prior to surgery. The injections will be given to the anaesthetised child before the surgical procedure begins. The surgeon will perform the injections at three muscle groups around each hip: the adductors, hamstrings and iliopsoas muscles. Two units per kilogram will be given at each site. The maximum dose will be 12 units per kilogram or 500 units in total (whichever is the lesser), divided equally between six or three sites. A total of 2 ml of isotonic saline will be used to dissolve the contents of the trial vial of Botox. Each active drug vial will contain 100 iu of the Botox preparation. The volume injected will be dependent on the weight of the child. Injections of normal saline will be administered in those children randomised to the placebo arm of the study. |
| Saline | Placebo comparator | Drug: botulinum toxin intramuscular injectionThe injections will be given to the anaesthetised child before the surgical procedure begins. The surgeon will perform the injections at three muscle groups around each hip: the adductors, hamstrings and iliopsoas muscles. Injections of normal saline will be administered in those children randomised to the placebo arm of the study. The volume of normal saline injected will be equal to the volume of normal saline that would have been used if the child had been randomised to botulinum toxin. The injector will be blinded, as the solution is drawn up by unblinded nurses. |
Who may qualify
- Ages
- 2 to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- The child has displaced hips requiring bony orthopaedic surgery (osteotomy) due to cerebral palsy (appendix 2).
- The child is between the ages of 2 and 15 years (inclusive).
- The child has a GMFCS level of IV or V
- The child has a diagnosis of hypertonic cerebral palsy (or a diagnosis consistent with this nomenclature)
- The child does not communicate verbally
Key exclusion criteria (6 listed)
- The child is younger than 2 years or older than 15 years
- The child has an acute and current systemic infection or illness
- The child has had botulinum toxin injections within the past 4 months
- The child has had a previous reaction to botulinum toxin
- The child has received or is likely to receive, at the time of trial drug or placebo administration, medications which might interact with botulinum toxin (this does not apply to any drugs at present)
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 |
|---|---|---|
| botulinum toxin intramuscular injectionAlso: Botox, Allergan.A single dose of active drug or placebo will be administered immediately prior to surgery. The injections will be given to the anaesthetised child before the surgical procedure begins. The surgeon will perform the injections at three muscle groups around each hip: the adductors, hamstrings and iliopsoas muscles. Two units per kilogram will be given at each site. The maximum dose will be 12 units per kilogram or 500 units in total (whichever is the lesser), divided equally between six or three sites. Each active drug vial will contain 100 iu of the Botox preparation. The volume injected will be dependent on the weight of the child. Injections of normal saline will be administered in those children randomised to the placebo. | Drug | Botulinum Toxin TypeA, Saline |
Primary outcome
Paediatric Pain Profile
Time frame: 6 weeks post-op
The primary endpoint is the change in pain score during the six weeks following the operation. Pain will be measured using a validated questionnaire, the Paediatric Pain Profile. This scores pain by rating twenty different items of observed behaviour on an ordinal scale of 0 to 3 with a composite score of 0 to 60. It has been validated in children with severe cerebral palsy.
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 1 May 2015.
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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.
Rebecca Newton study director
King's Health Partners Clinical Trials Office
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing botulinum toxin intramuscular injection in people with Cerebral Palsy and Post-operative Pain, run by Guy's and St Thomas' NHS Foundation Trust at 1 site 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 6 inclusion and 6 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 1 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Paediatric Pain Profile (time frame: 6 weeks post-op). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 May 2015.