Low Back PainPhase 3PredictioNCT01179828
Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain (Predictio)
A Phase 3 study testing Oxycodone 15mg, Clobazam and Imipramine in people with Low Back Pain, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
Drug therapy in patients with chronic low back pain is a major challenge for physicians. One of the problems is the lacking knowledge in prediction of drug efficacy in a chosen patient. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Low Back Pain
- What is being tested?
- Oxycodone 15mg, Clobazam and Imipramine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jul 2010to Dec 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Low back pain with NRS>2
- Chronic low back pain since more than 6 months
Who cannot join
- pregnancy
- use of pain medication other than paracetamol and ibuprofen in the last 7 days
- suspicion of radicular pain
- suspicion of intervertebral disk herniation
- foraminal intervertebral stenosis
- suspicion of polyneuropathy
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- diabetes
- parkinson disease
- alzheimer disease
- glaucoma
- prostata hyperplasia or voiding problems
- known heart rhythm problems
- heart insufficiency NYHA 3-4
- Systemic inflammatory disease
- Ongoing oncologic disease
- drug or alcohol abuse
- Significant depressive disease (BDI-FS>9)
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Andreas Siegenthaler
Dep. of Anesthesiolgy and Pain Therapy, Bern University Hospital, 3010 Bern
About this study
Official title: Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain
Drug therapy in patients with chronic low back pain is a major challenge for physicians. One of the problems is the lacking knowledge in prediction of drug efficacy in a chosen patient. Usually one of the classes of pain medication is given to patients with a similar clinical picture, although different pain mechanisms may be responsible for this clinical picture.
Another reason for variable drug efficacy are genetic polymorphisms, this may be the reason why an unique drug produces different responses (from a lacking analgesic effect up to excessive effect or side-effects.
Quantitative sensory testing is a method that documents alterations in the pain perception system. Linking genetic polymorphisms to quantitative sensory testing may give us a tool for anticipation of drug efficacy.
Read the detailed description
Background
Drug therapy is an essential part of pain treatment. However, only a minor part of pain patients benefits from the available treatments or is able to tolerate the drugs. One important limitation of drug therapy is lack of instruments to predict their effect. Indeed, in clinical practice "classes" of drugs (e.g. antidepressants) are given to "classes" of patients (e.g. neuropathic pain patients). However, within those classes of patients very different pain mechanisms are likely to underlie the pain condition in different patients. If drugs affect part of these mechanisms, they will not work in all patients. Another reason for variability in drug responses is genetic variation leading to a spectrum of different responses to analgesics, from lack of efficacy to exaggerated responses, up to intolerable adverse effects.
Quantitative sensory testing comprises methods that document alterations and reorganization of the nociceptive system. Measuring an abnormal result in a chronic pain patient may provide us with the information that the underlying pain pathways somehow must be altered. An essential question is whether this information can be linked to drug efficacy in a mechanism-based treatment approach. A further important question is whether assessing genetic polymorphisms can explain different drug effects and hence help selecting the appropriate therapeutic strategy for individual patients.
Objective
We will test the hypothesis that there is a correlation between disturbances in specific pain mechanisms as assessed by quantitative sensory tests and analgesic efficacy after single-dose drug administration in patients with chronic low back pain. Genetic factors affecting drug metabolism and pain sensitivity will be analyzed as additional explanatory variables for drug efficacy.
Methods
Quantitative sensory testing: Heat pain threshold and tolerance, Ice water testing with central modulation of nociceptive input (DNIC), electrical pain detection and temporal summation (skin probe), pressure algometry with pain detection and threshold Drugs investigated: Imipramine, Oxycodone, Clobazam Blood samples: pharmacogenetics: Cytochrome variants CYP2D6, CYP2C19, CYP3A4, COMT haplotypes, CGH-1 variants, A118G of mu opioid receptor gene variants pharmacokinetics: kinetics of imipramine and desipramine
- Conditions
- Low Back Pain
- Being tested
- Oxycodone 15mg, Clobazam, Imipramine, Tolterodine
- Keywords
- Quantitative sensory testing, Drug efficacy, Low back pain syndrome, Imipramine, Oxycodone, Clobazam, Tolterodine
- Medical subject headings
- Low Back Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oxycodone 15mgDrug
15mg single administration p.o.
ClobazamDrug
20mg single administration p.o.
ImipramineDrug
75mg single administration p.o.
TolterodineDrug
1 mg single administration p.o.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Oxycodone 15mg Receives: Drug: Oxycodone 15mg |
| 2 | Active comparator | Clobazam 20mg Receives: Drug: Clobazam |
| 3 | Active comparator | Imipramine 75mg Receives: Drug: Imipramine |
| 4 | Placebo comparator | Tolterodine 1mg Receives: Drug: Tolterodine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in NRS(pain scale) between measurement after and before drug administration
Measured: 07/2012
Secondary outcomes (4)
Patients global impression of change scale after drug administration
Measured: 07/2012
Pharmacogenetic variables(see before)
Measured: 07/2012
Pharmacokinetics: measure of Imipramine and desipramine blood levels
Measured: 07/2012
Reliability of repeated quantitative sensory testing in the same patient
Measured: 12/2010
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2010 (estimated)
- Study startJul 2010
- Primary completionApr 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Low Back PainStudies 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 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bern, University of Zurich, Aalborg University
- Investigators
- Michele Curatolo, Prof, Study chair, University Hospital Bern, SwitzerlandAndreas Siegenthaler, Dr Med, Study director, University Hospital Bern, SwitzerlandPascal H Vuilleumier, Dr Med, Principal investigator, University Hospital Bern, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01179828
- Sponsor's protocol ID
- KEK 213/09
- Other IDs
- grant: SPUM no. 33CM30_124117
- Acronym
- Predictio
- Status last verified
- Apr 2016
- First submitted
- 10 Aug 2010
- Last updated
- 6 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 2007 Oct 17;2007(4):CD005454. doi: 10.1002/14651858.CD005454.pub2.
PubMed 17943857Arendt-Nielsen L, Yarnitsky D. Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera. J Pain. 2009 Jun;10(6):556-72. doi: 10.1016/j.jpain.2009.02.002. Epub 2009 Apr 19.
PubMed 19380256Foulkes T, Wood JN. Pain genes. PLoS Genet. 2008 Jul 25;4(7):e1000086. doi: 10.1371/journal.pgen.1000086.
PubMed 18654615Curatolo M, Arendt-Nielsen L, Petersen-Felix S. Central hypersensitivity in chronic pain: mechanisms and clinical implications. Phys Med Rehabil Clin N Am. 2006 May;17(2):287-302. doi: 10.1016/j.pmr.2005.12.010.
PubMed 16616268Markenson JA, Croft J, Zhang PG, Richards P. Treatment of persistent pain associated with osteoarthritis with controlled-release oxycodone tablets in a randomized controlled clinical trial. Clin J Pain. 2005 Nov-Dec;21(6):524-35. doi: 10.1097/01.ajp.0000146215.86038.38.
PubMed 16215338Schliessbach J, Siegenthaler A, Butikofer L, Vuilleumier P, Juni P, Arendt-Nielsen L, Curatolo M. Quantitative sensory tests fairly reflect immediate effects of oxycodone in chronic low-back pain. Scand J Pain. 2017 Oct;17:107-115. doi: 10.1016/j.sjpain.2017.07.004. Epub 2017 Aug 9.
PubMed 28850362Siegenthaler A, Schliessbach J, Vuilleumier PH, Juni P, Zeilhofer HU, Arendt-Nielsen L, Curatolo M. Linking altered central pain processing and genetic polymorphism to drug efficacy in chronic low back pain. BMC Pharmacol Toxicol. 2015 Sep 16;16:23. doi: 10.1186/s40360-015-0023-z.
PubMed 26376691
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain
- ClinicalTrials.gov ID
- NCT01179828
- Acronym / sponsor ID
- Predictio / KEK 213/09
- Conditions
- Low Back Pain
- Keywords
- Quantitative sensory testing, Drug efficacy, Low back pain syndrome, Imipramine, Oxycodone, Clobazam, Tolterodine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- University of Bern, University of Zurich, Aalborg University
- Study start
- Jul 2010
- Primary completion
- Apr 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 11 Aug 2010 (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.
Drug therapy in patients with chronic low back pain is a major challenge for physicians. One of the problems is the lacking knowledge in prediction of drug efficacy in a chosen patient. Usually one of the classes of pain medication is given to patients with a similar clinical picture, although different pain mechanisms may be responsible for this clinical picture.
Another reason for variable drug efficacy are genetic polymorphisms, this may be the reason why an unique drug produces different responses (from a lacking analgesic effect up to excessive effect or side-effects.
Quantitative sensory testing is a method that documents alterations in the pain perception system. Linking genetic polymorphisms to quantitative sensory testing may give us a tool for anticipation of drug efficacy.
Detailed description
Background
Drug therapy is an essential part of pain treatment. However, only a minor part of pain patients benefits from the available treatments or is able to tolerate the drugs. One important limitation of drug therapy is lack of instruments to predict their effect. Indeed, in clinical practice "classes" of drugs (e.g. antidepressants) are given to "classes" of patients (e.g. neuropathic pain patients). However, within those classes of patients very different pain mechanisms are likely to underlie the pain condition in different patients. If drugs affect part of these mechanisms, they will not work in all patients. Another reason for variability in drug responses is genetic variation leading to a spectrum of different responses to analgesics, from lack of efficacy to exaggerated responses, up to intolerable adverse effects.
Quantitative sensory testing comprises methods that document alterations and reorganization of the nociceptive system. Measuring an abnormal result in a chronic pain patient may provide us with the information that the underlying pain pathways somehow must be altered. An essential question is whether this information can be linked to drug efficacy in a mechanism-based treatment approach. A further important question is whether assessing genetic polymorphisms can explain different drug effects and hence help selecting the appropriate therapeutic strategy for individual patients.
Objective
We will test the hypothesis that there is a correlation between disturbances in specific pain mechanisms as assessed by quantitative sensory tests and analgesic efficacy after single-dose drug administration in patients with chronic low back pain. Genetic factors affecting drug metabolism and pain sensitivity will be analyzed as additional explanatory variables for drug efficacy.
Methods
Quantitative sensory testing: Heat pain threshold and tolerance, Ice water testing with central modulation of nociceptive input (DNIC), electrical pain detection and temporal summation (skin probe), pressure algometry with pain detection and threshold Drugs investigated: Imipramine, Oxycodone, Clobazam Blood samples: pharmacogenetics: Cytochrome variants CYP2D6, CYP2C19, CYP3A4, COMT haplotypes, CGH-1 variants, A118G of mu opioid receptor gene variants pharmacokinetics: kinetics of imipramine and desipramine
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Oxycodone 15mgOxycodone 15mg |
| 2 | Active comparator | Drug: ClobazamClobazam 20mg |
| 3 | Active comparator | Drug: ImipramineImipramine 75mg |
| 4 | Placebo comparator | Drug: TolterodineTolterodine 1mg |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Low back pain with NRS>2
- Chronic low back pain since more than 6 months
Key exclusion criteria (17 listed)
- pregnancy
- use of pain medication other than paracetamol and ibuprofen in the last 7 days
- suspicion of radicular pain
- suspicion of intervertebral disk herniation
- foraminal intervertebral stenosis
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 |
|---|---|---|
| Oxycodone 15mg15mg single administration p.o. | Drug | 1 |
| Clobazam20mg single administration p.o. | Drug | 2 |
| Imipramine75mg single administration p.o. | Drug | 3 |
| Tolterodine1 mg single administration p.o. | Drug | 4 |
Primary outcome
Difference in NRS(pain scale) between measurement after and before drug administration
Time frame: 07/2012
4 secondary outcomes
Patients global impression of change scale after drug administration
Time frame: 07/2012
Pharmacogenetic variables(see before)
Time frame: 07/2012
Pharmacokinetics: measure of Imipramine and desipramine blood levels
Time frame: 07/2012
Reliability of repeated quantitative sensory testing in the same patient
Time frame: 12/2010
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 6 Apr 2016.
- Background: PubMed 17943857Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 2007 Oct 17;2007(4):CD005454. doi: 10.1002/14651858.CD005454.pub2.
- Results publication: PubMed 19380256Arendt-Nielsen L, Yarnitsky D. Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera. J Pain. 2009 Jun;10(6):556-72. doi: 10.1016/j.jpain.2009.02.002. Epub 2009 Apr 19.
- Results publication: PubMed 18654615Foulkes T, Wood JN. Pain genes. PLoS Genet. 2008 Jul 25;4(7):e1000086. doi: 10.1371/journal.pgen.1000086.
- Results publication: PubMed 16616268Curatolo M, Arendt-Nielsen L, Petersen-Felix S. Central hypersensitivity in chronic pain: mechanisms and clinical implications. Phys Med Rehabil Clin N Am. 2006 May;17(2):287-302. doi: 10.1016/j.pmr.2005.12.010.
- Results publication: PubMed 16215338Markenson JA, Croft J, Zhang PG, Richards P. Treatment of persistent pain associated with osteoarthritis with controlled-release oxycodone tablets in a randomized controlled clinical trial. Clin J Pain. 2005 Nov-Dec;21(6):524-35. doi: 10.1097/01.ajp.0000146215.86038.38.
- Derived from this study: PubMed 28850362Schliessbach J, Siegenthaler A, Butikofer L, Vuilleumier P, Juni P, Arendt-Nielsen L, Curatolo M. Quantitative sensory tests fairly reflect immediate effects of oxycodone in chronic low-back pain. Scand J Pain. 2017 Oct;17:107-115. doi: 10.1016/j.sjpain.2017.07.004. Epub 2017 Aug 9.
- Derived from this study: PubMed 26376691Siegenthaler A, Schliessbach J, Vuilleumier PH, Juni P, Zeilhofer HU, Arendt-Nielsen L, Curatolo M. Linking altered central pain processing and genetic polymorphism to drug efficacy in chronic low back pain. BMC Pharmacol Toxicol. 2015 Sep 16;16:23. doi: 10.1186/s40360-015-0023-z.
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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.
Michele Curatolo, Prof study chair
University Hospital Bern, Switzerland
Andreas Siegenthaler, Dr Med study director
University Hospital Bern, Switzerland
Pascal H Vuilleumier, Dr Med principal investigator
University Hospital Bern, Switzerland
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 Oxycodone 15mg, Clobazam and Imipramine in people with Low Back Pain, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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 2 inclusion and 17 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 6 Apr 2016. 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 Switzerland. 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?
Difference in NRS(pain scale) between measurement after and before drug administration (time frame: 07/2012). 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 NCT01179828, which also lists 7 linked publications.
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 6 Apr 2016.