Diabetic PolyneuropathyPhase 4NCT01116531
Efficacy, Safety, Tolerability and Pharmacokinetics of Concomitant Administration of Tramadol With Duloxetine or Pregabalin
A Phase 4 study testing Tramadol, Duloxetine and Pregabalin in people with Diabetic Polyneuropathy and Postherpetic Neuralgia, run by Turku University Hospital at 1 site in Finland.
Trial summary
Tramadol is an opioid analgesic, which is widely used in the treatment of acute and neuropathic pain. Treatment of neuropathic pain often requires a combination of pain medications due to the complex nature of neuropathic pain and frequent inadequate response to drug treatment. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diabetic Polyneuropathy, Postherpetic Neuralgia
- What is being tested?
- Tramadol, Duloxetine and Pregabalin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteFinland
- Study dates
- Apr 2010to Dec 2012
- Phase
- Phase 4
- 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
- Chronic (≥ 6 months) neuropathic pain due to postherpetic neuralgia or diabetic polyneuropathy
- Pain intensity ≥ 4 on a numerical scale of 0-10
- Informed consent
Who cannot join
- Clinically significant abnormalities in laboratory screening
- Pregnancy
- Depression
- Use of strong opioids (morphine, oxycodone, fentanyl, hydromorphone, methadone)
- A previous history of intolerance or allergy to the study drugs or to related compounds and additives
- Existing or history of seizures, haematological disorders, clinically significant renal, hepatic, respiratory, cardiac or psychiatric disease, dementia, drug allergy
- Previous or present alcoholism, drug abuse, psychological or other emotional problems or cognitive impairment that are likely to invalidate informed consent or limit the ability of the subject to comply with protocol requirements
- Concomitant drug therapy known to cause significant enzyme induction or inhibition of CYP 1A2, 2D6, 3A4, 2B6, drugs metabolised by CYP2D6 enzyme, antidepressants, MAO-inhibitors, non-steroidal anti-inflammatory analgesics.
Trial locations and contacts
1 site in 1 country.
Finland1 site
Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital
Turku, 20520
About this study
Official title: Efficacy, Safety, Tolerability and Pharmacokinetics of Concomitant Administration of Tramadol With Duloxetine or Pregabalin: a Randomized Controlled Flexible-dose Study in Patients With Neuropathic Pain
Tramadol is an opioid analgesic, which is widely used in the treatment of acute and neuropathic pain. Treatment of neuropathic pain often requires a combination of pain medications due to the complex nature of neuropathic pain and frequent inadequate response to drug treatment. Common drugs used concomitantly with tramadol are SNRI antidepressant duloxetine and anticonvulsants such as pregabalin. Both tramadol and duloxetine have serotonergic effects and duloxetine has also a potential to inhibit metabolism of tramadol. The objective of the study is to investigate the pharmacokinetics and pharmacodynamic interaction of oral tramadol with duloxetine and pregabalin in patients with chronic neuropathic pain due to postherpetic neuralgia or diabetic polyneuropathy. All subjects will receive tramadol and duloxetine or tramadol and pregabalin in a randomized double-blind order. Primary end point is O-desmethyltramadol concentration.
- Conditions
- Diabetic Polyneuropathy, Postherpetic Neuralgia
- Being tested
- Tramadol, Duloxetine, Pregabalin
- Keywords
- Pharmacokinetics, Pharmacodynamics, Interaction, tramadol, duloxetine, pregabalin
- Medical subject headings
- Diabetic Neuropathies, Neuralgia, Postherpetic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TramadolDrug
Initial dose of oral tramadol (depottabl Tramal retard, Orionpharma, Finland) will be 100mg once daily. If the subject is currently on opioid treatment with codeine, tramadol or buprenorphine, the opioid treatment will be stopped, and an equal dose of tramadol will be used as the initial dose. The dose will be titrated on visits V2 and V3 based on the adequacy of pain relief and tolerability. If pain intensity ≥ 4 on a numeric rating scale of 0-10 during V2 and V3 and tramadol is well tolerated, the daily dose will be increased by 100mg. The maximum daily dose of 400 mg tramadol will not be exceeded. If the subject does not tolerate the initial dose of tramadol, he/she will be dropped out of the study and replaced by another patient.
DuloxetineDrug
The initial dose of duloxetine (Cymbalta, Eli Lilly, USA) will be 30mg once daily. The dose will be titrated on V2 based on the adequacy of pain relief and tolerability. If pain intensity during V2 is < 4 on a scale of 0-10, the dose of duloxetine dose will be 30mg daily throughout the study. If pain intensity is ≥ 4 on a numeric rating scale of 0-10 and duloxetine is well tolerated, the daily dose will be increased to 60mg once daily. If the subject does not tolerate the initial dose of duloxetine, he/she will be dropped out of the study and replaced by another patient.
PregabalinDrug
The initial dose of pregabalin (Lyrica, Pfizer, USA) will be 75mg twice a day. The dose will be titrated on V2 based on the adequacy of pain relief and tolerability. If pain intensity during V2 is < 4 on a scale of 0-10, the initial dose of pregabalin dose will be continued. If pain intensity is ≥ 4 on a numeric rating scale of 0-10 and pregabalin is well tolerated, the daily dose will be increased to 150mg twice a day. If the subject does not tolerate the initial dose of pregabalin, he/she will be dropped out of the study and replaced by another patient.
| Study group | Role | What they receive |
|---|---|---|
| Duloxetine and tramadol | Active comparator | To ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy. Receives: Drug: Tramadol; Drug: Duloxetine |
| Pregabalin and tramadol | Active comparator | To ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy. Receives: Drug: Tramadol; Drug: Pregabalin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of O-desmethyltramadol
Measured: 3 weeks
Secondary outcomes (6)
Plasma 5-HT concentration
Measured: baseline, 1, 2 and 3 weeks
Platelet function
Measured: baseline and 3 weeks
Pain intensity
Pain intensity will be rated by the subjects on a numerical 11-point rating scale of 0-10 (NRS) with 0 meaning "no pain" and 10 meaning "pain as bad as you can imagine". The subjects will be asked to rate pain intensity on the average over the past 24 hours. Pain intensity will be recorded at each study visit and daily by the subject using a pain diary.
Measured: daily for 3 weeks
Use of rescue medication
Measured: 1,2 and 3 weeks
Behavioral serotonergic effects
Measured: 1, 2 and 3 weeks
Concentration of O-desmethyltramadol
Measured: baseline, 1 and 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2010 (estimated)
- Study startApr 2010
- Primary completionDec 2012
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic PolyneuropathyStudies of the same condition, open and under way.
- More trials run by Turku University HospitalThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Turku University Hospital
- Sponsor type
- Other government
- Collaborators
- University of Helsinki
- Investigators
- Klaus T Olkkola, MD,PhD,Prof, Principal investigator, Turku University Hospital and Turku University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01116531
- Sponsor's protocol ID
- 60/180/2009
- Status last verified
- May 2013
- First submitted
- 19 Apr 2010
- Last updated
- 31 May 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy, Safety, Tolerability and Pharmacokinetics of Concomitant Administration of Tramadol With Duloxetine or Pregabalin: a Randomized Controlled Flexible-dose Study in Patients With Neuropathic Pain
- ClinicalTrials.gov ID
- NCT01116531
- Acronym / sponsor ID
- 60/180/2009
- Conditions
- Diabetic Polyneuropathy, Postherpetic Neuralgia
- Keywords
- Pharmacokinetics, Pharmacodynamics, Interaction, tramadol, duloxetine, pregabalin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Turku University HospitalOther government
- Collaborators
- University of Helsinki
- Study start
- Apr 2010
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (estimated)
- First posted
- 5 May 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.
Tramadol is an opioid analgesic, which is widely used in the treatment of acute and neuropathic pain. Treatment of neuropathic pain often requires a combination of pain medications due to the complex nature of neuropathic pain and frequent inadequate response to drug treatment. Common drugs used concomitantly with tramadol are SNRI antidepressant duloxetine and anticonvulsants such as pregabalin. Both tramadol and duloxetine have serotonergic effects and duloxetine has also a potential to inhibit metabolism of tramadol. The objective of the study is to investigate the pharmacokinetics and pharmacodynamic interaction of oral tramadol with duloxetine and pregabalin in patients with chronic neuropathic pain due to postherpetic neuralgia or diabetic polyneuropathy. All subjects will receive tramadol and duloxetine or tramadol and pregabalin in a randomized double-blind order. Primary end point is O-desmethyltramadol concentration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Duloxetine and tramadol | Active comparator | Drug: Tramadol, Drug: DuloxetineTo ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy. |
| Pregabalin and tramadol | Active comparator | Drug: Tramadol, Drug: PregabalinTo ascertain the double-blinding of subjects and investigators, duloxetine and pregabalin will be administered as 2 similar capsules twice a day. Each of these capsules will contain either 30mg of duloxetine, 75 mg of pregabalin or placebo. Capsules will be prepared at the hospital pharmacy. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Chronic (≥ 6 months) neuropathic pain due to postherpetic neuralgia or diabetic polyneuropathy
- Pain intensity ≥ 4 on a numerical scale of 0-10
- Informed consent
Key exclusion criteria (8 listed)
- Clinically significant abnormalities in laboratory screening
- Pregnancy
- Depression
- Use of strong opioids (morphine, oxycodone, fentanyl, hydromorphone, methadone)
- A previous history of intolerance or allergy to the study drugs or to related compounds and additives
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 |
|---|---|---|
| TramadolInitial dose of oral tramadol (depottabl Tramal retard, Orionpharma, Finland) will be 100mg once daily. If the subject is currently on opioid treatment with codeine, tramadol or buprenorphine, the opioid treatment will be stopped, and an equal dose of tramadol will be used as the initial dose. The dose will be titrated on visits V2 and V3 based on the adequacy of pain relief and tolerability. If pain intensity ≥ 4 on a numeric rating scale of 0-10 during V2 and V3 and tramadol is well tolerated, the daily dose will be increased by 100mg. The maximum daily dose of 400 mg tramadol will not be exceeded. If the subject does not tolerate the initial dose of tramadol, he/she will be dropped out of the study and replaced by another patient. | Drug | Duloxetine and tramadol, Pregabalin and tramadol |
| DuloxetineThe initial dose of duloxetine (Cymbalta, Eli Lilly, USA) will be 30mg once daily. The dose will be titrated on V2 based on the adequacy of pain relief and tolerability. If pain intensity during V2 is < 4 on a scale of 0-10, the dose of duloxetine dose will be 30mg daily throughout the study. If pain intensity is ≥ 4 on a numeric rating scale of 0-10 and duloxetine is well tolerated, the daily dose will be increased to 60mg once daily. If the subject does not tolerate the initial dose of duloxetine, he/she will be dropped out of the study and replaced by another patient. | Drug | Duloxetine and tramadol |
| PregabalinThe initial dose of pregabalin (Lyrica, Pfizer, USA) will be 75mg twice a day. The dose will be titrated on V2 based on the adequacy of pain relief and tolerability. If pain intensity during V2 is < 4 on a scale of 0-10, the initial dose of pregabalin dose will be continued. If pain intensity is ≥ 4 on a numeric rating scale of 0-10 and pregabalin is well tolerated, the daily dose will be increased to 150mg twice a day. If the subject does not tolerate the initial dose of pregabalin, he/she will be dropped out of the study and replaced by another patient. | Drug | Pregabalin and tramadol |
Primary outcome
Concentration of O-desmethyltramadol
Time frame: 3 weeks
6 secondary outcomes
Plasma 5-HT concentration
Time frame: baseline, 1, 2 and 3 weeks
Platelet function
Time frame: baseline and 3 weeks
Pain intensity
Time frame: daily for 3 weeks
Use of rescue medication
Time frame: 1,2 and 3 weeks
Behavioral serotonergic effects
Time frame: 1, 2 and 3 weeks
Concentration of O-desmethyltramadol
Time frame: baseline, 1 and 2 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2013.
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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.
Klaus T Olkkola, MD,PhD,Prof principal investigator
Turku University Hospital and Turku University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tramadol, Duloxetine and Pregabalin in people with Diabetic Polyneuropathy and Postherpetic Neuralgia, run by Turku University Hospital at 1 site in Finland.
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 3 inclusion and 8 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: withdrawn, as of the sponsor's last update on 31 May 2013. 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 Finland. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was withdrawn before enrolling participants, so there are no results.
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?
Concentration of O-desmethyltramadol (time frame: 3 weeks). 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 31 May 2013.