Pain, NeuropathicPhase 1NCT01485185
Gabapentin and Donepezil Combination on Experimental Human Pain Models
A Phase 1 study testing Gabapentin lower dose, Donepezil and Gabapentin higher dose in people with Pain, Neuropathic, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
This study will compare the effects of gabapentin alone, and gabapentin + donepezil given together in two types of experimental electrical pain tests in up to 48 healthy male subjects (after 24 recruited in the first cohort an interim analysis will be performed). Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pain, Neuropathic
- What is being tested?
- Gabapentin lower dose, Donepezil and Gabapentin higher dose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Oct 2011to 3 Jul 2012
- Phase
- Phase 1
- 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 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- Body weight ≥ 50 Kilogram (kg) and BMI within the range 18.5-29.9 Killogram per square meter (kg/m2) (inclusive).
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, psychiatric history, psychiatric evaluation, laboratory tests and cardiac monitoring.
- Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin ≤ 1.5x Upper Limit of Normal (ULN)
- QT duration corrected for heart rate by Bazett's formula (QTcB) or QT duration corrected for heart rate by Fridericia's formula (QTcF) < 450 milli second (msec).
Who cannot join
- The subject has either a previous disease or current medical condition, which as judged by the Investigator, may compromise safety or affect the interpretation of efficacy data.
- History of known or suspected seizures, including infantile febrile, unexplained significant and recent loss of consciousness or history of significant head trauma with loss of consciousness or a family history (first degree relative) of epilepsy or seizures (fits).
- Abnormalities in 12-lead Electrocardiogram (ECG)
- Systolic blood pressure (BP) below 90 or above 160mm Hg, or diastolic blood pressure below 50 or above 100 millimeters of mercury (mmHg).
- History of sensitivity to any of the study medications
- History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >21 units. One unit is equivalent to 8 g of alcohol: a half-pint (~240 millil litre [ml]) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
Show all 19Show fewer
- A positive pre-study drug/alcohol screen at the screening visit.
- Excessive caffeine drinkers (~5 or more cups a day) .
- Excessive smokers (>5 /day)
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to screening, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- Use of any topical steroid or capsaicin preparations in the previous 30 days to screening, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- The subject is needle phobic
- The subject is unable to tolerate the electrical hyperalgesia model or nerve stimulation, including anxiety or atypical response to the stimulation on the training at the screening visit.
- The subject does not produce an area of allodynia or hyperalgesia to the electrical hyperalgesia model during the screening session.
- Subject who, in the investigator/designee's judgement, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behaviour and/or any evidence of suicidal ideation on any questionnaires e.g. type 4 or 5 on the C-SSRS in the last 6 months.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the baseline session in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 84 day period.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Unwillingness or inability to follow the procedures outlined in the protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double Blind, Placebo Controlled Study to Investigate the Effect of Donepezil and Gabapentin Combination on an Experimental Pain Model in Healthy Subjects
This study will compare the effects of gabapentin alone, and gabapentin + donepezil given together in two types of experimental electrical pain tests in up to 48 healthy male subjects (after 24 recruited in the first cohort an interim analysis will be performed).
The study is a randomized, double blind, placebo controlled, 3 was cross-over design study with incomplete block design and 4 treatment options. Placebo, gabapentin alone (lower dose and higher dose) or gabapentin (lower dose) with donepezil.
Read the detailed description
This study will compare the effects of gabapentin alone, and gabapentin + donepezil given together in two types of experimental electrical pain tests which will be conducted on the forearm and the lower leg, in 24 healthy male subjects initially. Gabapentin (a drug for treatment of seizure disorders) is one of the drugs being used for the treatment of pain caused by the damage to the nerves. Donepezil is a treatment to improve memory in patients with Alzheimer's disease. 24 more subjects may be recruited following a formal analysis during the trial (called interim analysis), if required for optimal scientific value. The study consists of 1 screening visit,1 visit to establish the baseline pain recordings before any treatment is given, then 3 treatment sessions, followed by a followup visit. Each treatment session consists of 12 days of dosing at home and 2 inpatient days for dosing and pain tests. Each volunteer takes part in 3 treatment sessions. In total, the study will last 15 weeks for each volunteer. There will be 4 treatment options: placebo, higher dose of gabapentin, low dose of gabapentin, low dose of gabapentin + donepezil. All subjects will receive the last two options and one out of the first two options, in a random order selected by a computer before the study starts; neither the volunteers nor the persons conducting the pain assessments nor the study team will know which treatment the volunteers receive during the visits (known as a randomised, double-blind study). The study will be conducted in a specialist clinical research unit with adequate facilities with regard to safety and compliance. The results of the tests in the study will help to understand the effects of gabapentin and donepezil together to design future clinical trials.
- Conditions
- Pain, Neuropathic
- Being tested
- Gabapentin lower dose, Donepezil, Placebo (Dop), Placebo (Gaba), Gabapentin higher dose
- Keywords
- Donepezil, allodynia, Gabapentin, Sural nerve stimulation, Electrical hyperalgesia
- Medical subject headings
- Neuralgia, Hyperalgesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gabapentin lower doseDrug
Repeat, oral dose
DonepezilDrug
Repeat, oral dose
Placebo (Dop)Other
Placebo to donepezil, Repeat, oral dose
Placebo (Gaba)Other
Placebo to gabapentin, Repeat, oral dose
Gabapentin higher doseDrug
Repeat, oral dose
| Study group | Role | What they receive |
|---|---|---|
| Gabapentin lower dose alone | Experimental | low dose Receives: Drug: Gabapentin lower dose |
| Gabapentin higher dose alone | Active comparator | higher dose Receives: Other: Placebo (Dop) |
| Gabapentin in combination with donepezil | Experimental | Gabapentin lower dose and donepezil Receives: Drug: Donepezil; Drug: Gabapentin higher dose |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo (Gaba) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area of pin-prick hyperalgesia
Change in Area between treatment arms (compared to baseline), measured during the electrical hyperalgesia model using 26 Milli Neuton(mN) von Frey filament
Measured: Change from baseline visit to day 14 of treatment sessions
Area of touch-evoked allodynia
Change in Area between treatment arms (compared to baseline), measured during the electrical hyperalgesia model using a cotton bud
Measured: Change from baseline visit to day 14 of treatment sessions
Secondary outcomes (5)
Pain threshold
Change in threshold between treatment arms (compared to baseline), measured from single electrical stimulation of sural nerve
Measured: Change from baseline visit to day 14 of treatment sessions
Ongoing pain intensity rating
Change in intensity between treatment arms (compared to baseline), measured from 11-point numeric rating scale (NRS) where 0=no pain, 10=maximum pain imaginable
Measured: Change from baseline visit to day 14 of treatment sessions
Pain Tolerance
Change in tolerance between treatment arms(compared to baseline), measured from single electrical stimulation of sural nerve
Measured: Change from baseline visit to day 14 of treatment sessions
Pain Temporal Summation
Change in temporal summation between treatment arms (compared to baseline), measured from repetitive electrical stimulation of sural nerve
Measured: Change from baseline visit to day 14 of treatment sessions
Intensity of flare
Change in intensity between treatment arms (compared to baseline), measured from Laser Doppler imaging evoked by electrical hyperalgesia model
Measured: Change from baseline visit to day 14 of treatment sessions
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2011 (estimated)
- Study start11 Oct 2011
- Primary completion3 Jul 2012
- Study completion3 Jul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pain, NeuropathicStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01485185
- Sponsor's protocol ID
- 115484
- Status last verified
- Jun 2017
- First submitted
- 29 Sep 2011
- Last updated
- 12 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Boyle Y, Fernando D, Kurz H, Miller SR, Zucchetto M, Storey J. The effect of a combination of gabapentin and donepezil in an experimental pain model in healthy volunteers: Results of a randomized controlled trial. Pain. 2014 Dec;155(12):2510-2516. doi: 10.1016/j.pain.2014.09.003. Epub 2014 Sep 10.
PubMed 25218827
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Placebo Controlled Study to Investigate the Effect of Donepezil and Gabapentin Combination on an Experimental Pain Model in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01485185
- Acronym / sponsor ID
- 115484
- Conditions
- Pain, Neuropathic
- Keywords
- Donepezil, allodynia, Gabapentin, Sural nerve stimulation, Electrical hyperalgesia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 11 Oct 2011 (actual)
- Primary completion
- 3 Jul 2012 (actual)
- Study completion
- 3 Jul 2012 (actual)
- First posted
- 5 Dec 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.
This study will compare the effects of gabapentin alone, and gabapentin + donepezil given together in two types of experimental electrical pain tests in up to 48 healthy male subjects (after 24 recruited in the first cohort an interim analysis will be performed).
The study is a randomized, double blind, placebo controlled, 3 was cross-over design study with incomplete block design and 4 treatment options. Placebo, gabapentin alone (lower dose and higher dose) or gabapentin (lower dose) with donepezil.
Detailed description
This study will compare the effects of gabapentin alone, and gabapentin + donepezil given together in two types of experimental electrical pain tests which will be conducted on the forearm and the lower leg, in 24 healthy male subjects initially. Gabapentin (a drug for treatment of seizure disorders) is one of the drugs being used for the treatment of pain caused by the damage to the nerves. Donepezil is a treatment to improve memory in patients with Alzheimer's disease. 24 more subjects may be recruited following a formal analysis during the trial (called interim analysis), if required for optimal scientific value. The study consists of 1 screening visit,1 visit to establish the baseline pain recordings before any treatment is given, then 3 treatment sessions, followed by a followup visit. Each treatment session consists of 12 days of dosing at home and 2 inpatient days for dosing and pain tests. Each volunteer takes part in 3 treatment sessions. In total, the study will last 15 weeks for each volunteer. There will be 4 treatment options: placebo, higher dose of gabapentin, low dose of gabapentin, low dose of gabapentin + donepezil. All subjects will receive the last two options and one out of the first two options, in a random order selected by a computer before the study starts; neither the volunteers nor the persons conducting the pain assessments nor the study team will know which treatment the volunteers receive during the visits (known as a randomised, double-blind study). The study will be conducted in a specialist clinical research unit with adequate facilities with regard to safety and compliance. The results of the tests in the study will help to understand the effects of gabapentin and donepezil together to design future clinical trials.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Gabapentin lower dose alone | Experimental | Drug: Gabapentin lower doselow dose |
| Gabapentin higher dose alone | Active comparator | Other: Placebo (Dop)higher dose |
| Gabapentin in combination with donepezil | Experimental | Drug: Donepezil, Drug: Gabapentin higher doseGabapentin lower dose and donepezil |
| Placebo | Placebo comparator | Other: Placebo (Gaba)Placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Male between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- Body weight ≥ 50 Kilogram (kg) and BMI within the range 18.5-29.9 Killogram per square meter (kg/m2) (inclusive).
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, psychiatric history, psychiatric evaluation, laboratory tests and cardiac monitoring.
- Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin ≤ 1.5x Upper Limit of Normal (ULN)
- QT duration corrected for heart rate by Bazett's formula (QTcB) or QT duration corrected for heart rate by Fridericia's formula (QTcF) < 450 milli second (msec).
Key exclusion criteria (19 listed)
- The subject has either a previous disease or current medical condition, which as judged by the Investigator, may compromise safety or affect the interpretation of efficacy data.
- History of known or suspected seizures, including infantile febrile, unexplained significant and recent loss of consciousness or history of significant head trauma with loss of consciousness or a family history (first degree relative) of epilepsy or seizures (fits).
- Abnormalities in 12-lead Electrocardiogram (ECG)
- Systolic blood pressure (BP) below 90 or above 160mm Hg, or diastolic blood pressure below 50 or above 100 millimeters of mercury (mmHg).
- History of sensitivity to any of the study medications
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 lower doseRepeat, oral dose | Drug | Gabapentin lower dose alone |
| DonepezilRepeat, oral dose | Drug | Gabapentin in combination with donepezil |
| Placebo (Dop)Placebo to donepezil, Repeat, oral dose | Other | Gabapentin higher dose alone |
| Placebo (Gaba)Placebo to gabapentin, Repeat, oral dose | Other | Placebo |
| Gabapentin higher doseRepeat, oral dose | Drug | Gabapentin in combination with donepezil |
Primary outcome
Area of pin-prick hyperalgesia
Time frame: Change from baseline visit to day 14 of treatment sessions
Change in Area between treatment arms (compared to baseline), measured during the electrical hyperalgesia model using 26 Milli Neuton(mN) von Frey filament
Area of touch-evoked allodynia
Time frame: Change from baseline visit to day 14 of treatment sessions
Change in Area between treatment arms (compared to baseline), measured during the electrical hyperalgesia model using a cotton bud
5 secondary outcomes
Pain threshold
Time frame: Change from baseline visit to day 14 of treatment sessions
Ongoing pain intensity rating
Time frame: Change from baseline visit to day 14 of treatment sessions
Pain Tolerance
Time frame: Change from baseline visit to day 14 of treatment sessions
Pain Temporal Summation
Time frame: Change from baseline visit to day 14 of treatment sessions
Intensity of flare
Time frame: Change from baseline visit to day 14 of treatment sessions
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 Jun 2017.
- Derived from this study: PubMed 25218827Boyle Y, Fernando D, Kurz H, Miller SR, Zucchetto M, Storey J. The effect of a combination of gabapentin and donepezil in an experimental pain model in healthy volunteers: Results of a randomized controlled trial. Pain. 2014 Dec;155(12):2510-2516. doi: 10.1016/j.pain.2014.09.003. Epub 2014 Sep 10.
- Results for study 115484 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gabapentin lower dose, Donepezil and Gabapentin higher dose in people with Pain, Neuropathic, run by GlaxoSmithKline 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 5 inclusion and 19 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 Jun 2017. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Area of pin-prick hyperalgesia (time frame: Change from baseline visit to day 14 of treatment sessions). The study lists 2 primary outcomes in all. 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 NCT01485185, which also lists 1 linked publication.
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 Jun 2017.