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| Name | Class |
|---|---|
| University of Helsinki | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tramadol | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of O-desmethyltramadol | 3 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma 5-HT concentration | baseline, 1, 2 and 3 weeks | |
| Platelet function | baseline and 3 weeks | |
| Pain intensity |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Klaus T Olkkola, MD,PhD,Prof | Turku University Hospital and Turku University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University and Turku University Hospital | Turku | 20520 | Finland |
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| Duloxetine | Drug | 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. |
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| Pregabalin | Drug | 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. |
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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. |
| daily for 3 weeks |
| Use of rescue medication | 1,2 and 3 weeks |
| Behavioral serotonergic effects | 1, 2 and 3 weeks |
| Concentration of O-desmethyltramadol | baseline, 1 and 2 weeks |
| ID | Term |
|---|---|
| D003929 | Diabetic Neuropathies |
| D051474 | Neuralgia, Postherpetic |
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D009437 | Neuralgia |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D014147 | Tramadol |
| D000068736 | Duloxetine Hydrochloride |
| D000069583 | Pregabalin |
| ID | Term |
|---|---|
| D003511 | Cyclohexanols |
| D000441 | Hexanols |
| D005233 | Fatty Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D004123 | Dimethylamines |
| D008744 | Methylamines |
| D000588 | Amines |
| D008055 | Lipids |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005680 | gamma-Aminobutyric Acid |
| D000613 | Aminobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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