Post-traumatic Neuropathic PainPhase 2NCT00967707
Population Pharmacokinetic-pharmacodynamic (PK-PD) Modeling of Co-administered Gabapentin in Neuropathic Pain
A Phase 2 study testing gabapentin and venlafaxine and gabapentin and donepezil in people with Post-traumatic Neuropathic Pain, run by Uppsala University at 1 site in Sweden.
Trial summary
The primary objective of this study is to develop a pharmacokinetic (PK) and a pharmacokinetic-pharmacodynamic (PK-PD) model for gabapentin in patients with neuropathic pain. The secondary objectives are to investigate whether adjuvant therapy of venlafaxine or donepezil contributes to 1) improved analgesic efficacy… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post-traumatic Neuropathic Pain
- What is being tested?
- gabapentin and venlafaxine and gabapentin and donepezil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSweden
- Study dates
- Aug 2009to Sep 2011
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of post-traumatic neuropathic pain
- Spontaneous pain intensity ≥ 40 on VAS or ≥ 4 on NRS
- Man or woman ≥ 18 years old
- Informed consent to study participation
Who cannot join
- Presence of other type of pain as strong as or stronger than the neuropathic pain
- Impaired kidney function (GFR < 30 ml/min)
- Uncontrolled cardiovascular disease/hypertonia
- Uncontrolled narrow-angle glaucoma
- Uncontrolled pulmonary disease
- Epilepsia
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- Pregnancy
- Nursing
- Woman of childbearing potential not using contraception or planning to become pregnant during the study period
- Disability to understand and cooperate with study procedures
- Allergy to study medications
- Concomitant participation in other clinical study
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Multidisciplinary Pain Centre, Uppsala University Hospital
Uppsala, 75185
About this study
Official title: Population Pharmacokinetic and Pharmacodynamic Modeling of Gabapentin in Neuropathic Pain - Effect of Adjuvant Pharmacotherapy
The primary objective of this study is to develop a pharmacokinetic (PK) and a pharmacokinetic-pharmacodynamic (PK-PD) model for gabapentin in patients with neuropathic pain.
The secondary objectives are to investigate whether adjuvant therapy of venlafaxine or donepezil contributes to 1) improved analgesic efficacy and 2) improved health-related quality of life (assessed by the SF-36 questionnaire) in neuropathic pain patients treated with gabapentin.
Read the detailed description
Neuropathic pain is estimated to affect 2-3 % of the population and the condition is difficult to treat with conventional analgesics. The drug of first choice is typically a tricyclic antidepressant drug (TCA) or the antiepileptic drug gabapentin. TCAs have well-documented effects, but the use is commonly interrupted due to intolerable adverse effects. Gabapentin, on the other hand, is generally well tolerated in patients. Clinical trials have proven that gabapentin is efficacious for neuropathic pain of various origins. Nevertheless, monotherapy is seldom sufficient for the management of severe neuropathic pain. Combination therapy, e.g. of gabapentin and an analgesic with complementary mechanism of action, may be a rational strategy to obtain improved results at lower doses and with fewer side effects. Although many neuropathic pain patients receive a combination of drugs, there is an absence of clinical evidence for optimal drug combinations.
Gabapentin binds to the alpha-2-delta subunit on presynaptic voltage-gated calcium channels, which results in modulation of the release of neurotransmitters from presynaptic nerve terminals. Recent studies in animal models of neuropathic pain have shown that gabapentin is effective on supraspinal structures, to activate the descending pain inhibitory noradrenergic-cholinergic cascade. Thus, it might be possible to potentiate the analgesic effect of gabapentin by concomitant administration of a drug able to prolong the action of noradrenaline or acetylcholine in the synapse cleft. In this study, the adjuvant effect of the noradrenaline and serotonin reuptake inhibitor venlafaxine and the cholinesterase inhibitor donepezil will be investigated in neuropathic pain patients treated with gabapentin.
The study consists of two periods. All patients are treated with gabapentin in the first period, and receive randomised adjuvant therapy of venlafaxine or donepezil in the second period. Repeated pain intensity ratings and blood samples for analysis of gabapentin plasma concentrations will be collected over one dosing interval of gabapentin at the end of each period.
Data will be analysed by means of nonlinear mixed effect modeling. The NONMEM programme will be used to develop models describing the PK and the PK-PD relationship of gabapentin in patients with neuropathic pain. The potential effect of concomitant treatment with venlafaxine or donepezil will be evaluated by covariate analysis in the developed PK and PK-PD models of gabapentin.
- Conditions
- Post-traumatic Neuropathic Pain
- Being tested
- gabapentin and venlafaxine, gabapentin and donepezil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gabapentin and venlafaxineDrug
Week 1-6: Gabapentin monotherapy (titration to individual maximum tolerated dose or maximum 800 mg 3 times daily).
Week 7-12: Venlafaxine 75 mg once daily is added.
gabapentin and donepezilDrug
Week 1-6: Gabapentin monotherapy (titration to individual maximum tolerated dose or maximum 800 mg 3 times daily).
Week 7-12: Donepezil 5 mg once daily is added.
| Study group | Role | What they receive |
|---|---|---|
| Gabapentin + venlafaxine | Active comparator | Not described Receives: Drug: gabapentin and venlafaxine |
| Gabapentin + donepezil | Active comparator | Not described Receives: Drug: gabapentin and donepezil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain intensity scorings on Numerical Rating Scale (NRS). Plasma concentrations of gabapentin.
Measured: 0 - 8 hours follwing dose intake of gabapentin. during steady state
Secondary outcomes (1)
Health-related quality of life assessed by SF-36. Pain according to McGill Pain Questionnaire.
Measured: Minimum 6 weeks following initiation of gabapentin and combination therapy, respectively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2009 (estimated)
- Study startAug 2009
- Primary completionApr 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-traumatic Neuropathic PainStudies of the same condition, open and under way.
- More trials run by Uppsala UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Uppsala University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen
- Responsible party
- Sponsor
- Investigators
- Stephen H. Butler, MD, Principal investigator, Uppsala University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00967707
- Sponsor's protocol ID
- GBPPKPD-09
- Other IDs
- EudraCT number 2009-010783-41
- Status last verified
- Sep 2011
- First submitted
- 27 Aug 2009
- Last updated
- 12 Oct 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Population Pharmacokinetic and Pharmacodynamic Modeling of Gabapentin in Neuropathic Pain - Effect of Adjuvant Pharmacotherapy
- ClinicalTrials.gov ID
- NCT00967707
- Acronym / sponsor ID
- GBPPKPD-09
- Conditions
- Post-traumatic Neuropathic Pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Uppsala UniversityUniversity, hospital or other
- Collaborators
- University of Copenhagen
- Study start
- Aug 2009
- Primary completion
- Apr 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 28 Aug 2009 (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.
The primary objective of this study is to develop a pharmacokinetic (PK) and a pharmacokinetic-pharmacodynamic (PK-PD) model for gabapentin in patients with neuropathic pain.
The secondary objectives are to investigate whether adjuvant therapy of venlafaxine or donepezil contributes to 1) improved analgesic efficacy and 2) improved health-related quality of life (assessed by the SF-36 questionnaire) in neuropathic pain patients treated with gabapentin.
Detailed description
Neuropathic pain is estimated to affect 2-3 % of the population and the condition is difficult to treat with conventional analgesics. The drug of first choice is typically a tricyclic antidepressant drug (TCA) or the antiepileptic drug gabapentin. TCAs have well-documented effects, but the use is commonly interrupted due to intolerable adverse effects. Gabapentin, on the other hand, is generally well tolerated in patients. Clinical trials have proven that gabapentin is efficacious for neuropathic pain of various origins. Nevertheless, monotherapy is seldom sufficient for the management of severe neuropathic pain. Combination therapy, e.g. of gabapentin and an analgesic with complementary mechanism of action, may be a rational strategy to obtain improved results at lower doses and with fewer side effects. Although many neuropathic pain patients receive a combination of drugs, there is an absence of clinical evidence for optimal drug combinations.
Gabapentin binds to the alpha-2-delta subunit on presynaptic voltage-gated calcium channels, which results in modulation of the release of neurotransmitters from presynaptic nerve terminals. Recent studies in animal models of neuropathic pain have shown that gabapentin is effective on supraspinal structures, to activate the descending pain inhibitory noradrenergic-cholinergic cascade. Thus, it might be possible to potentiate the analgesic effect of gabapentin by concomitant administration of a drug able to prolong the action of noradrenaline or acetylcholine in the synapse cleft. In this study, the adjuvant effect of the noradrenaline and serotonin reuptake inhibitor venlafaxine and the cholinesterase inhibitor donepezil will be investigated in neuropathic pain patients treated with gabapentin.
The study consists of two periods. All patients are treated with gabapentin in the first period, and receive randomised adjuvant therapy of venlafaxine or donepezil in the second period. Repeated pain intensity ratings and blood samples for analysis of gabapentin plasma concentrations will be collected over one dosing interval of gabapentin at the end of each period.
Data will be analysed by means of nonlinear mixed effect modeling. The NONMEM programme will be used to develop models describing the PK and the PK-PD relationship of gabapentin in patients with neuropathic pain. The potential effect of concomitant treatment with venlafaxine or donepezil will be evaluated by covariate analysis in the developed PK and PK-PD models of gabapentin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gabapentin + venlafaxine | Active comparator | Drug: gabapentin and venlafaxine |
| Gabapentin + donepezil | Active comparator | Drug: gabapentin and donepezil |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of post-traumatic neuropathic pain
- Spontaneous pain intensity ≥ 40 on VAS or ≥ 4 on NRS
- Man or woman ≥ 18 years old
- Informed consent to study participation
Key exclusion criteria (12 listed)
- Presence of other type of pain as strong as or stronger than the neuropathic pain
- Impaired kidney function (GFR < 30 ml/min)
- Uncontrolled cardiovascular disease/hypertonia
- Uncontrolled narrow-angle glaucoma
- Uncontrolled pulmonary disease
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 |
|---|---|---|
| gabapentin and venlafaxineWeek 1-6: Gabapentin monotherapy (titration to individual maximum tolerated dose or maximum 800 mg 3 times daily). Week 7-12: Venlafaxine 75 mg once daily is added. | Drug | Gabapentin + venlafaxine |
| gabapentin and donepezilWeek 1-6: Gabapentin monotherapy (titration to individual maximum tolerated dose or maximum 800 mg 3 times daily). Week 7-12: Donepezil 5 mg once daily is added. | Drug | Gabapentin + donepezil |
Primary outcome
Pain intensity scorings on Numerical Rating Scale (NRS). Plasma concentrations of gabapentin.
Time frame: 0 - 8 hours follwing dose intake of gabapentin. during steady state
1 secondary outcome
Health-related quality of life assessed by SF-36. Pain according to McGill Pain Questionnaire.
Time frame: Minimum 6 weeks following initiation of gabapentin and combination therapy, respectively
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 12 Oct 2011.
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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.
Stephen H. Butler, MD principal investigator
Uppsala University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing gabapentin and venlafaxine and gabapentin and donepezil in people with Post-traumatic Neuropathic Pain, run by Uppsala University at 1 site in Sweden.
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 4 inclusion and 12 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 12 Oct 2011. 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 Sweden. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Pain intensity scorings on Numerical Rating Scale (NRS). Plasma concentrations of gabapentin. (time frame: 0 - 8 hours follwing dose intake of gabapentin. during steady state). 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 12 Oct 2011.