Neuropathic PainPhase 4NCT03047278
Transporters for Organic Cations and Glycemic Control in Patients With Neuropathic Pain.
A Phase 4 study testing Serial Blood Samples, Serial Urine Samples and Gabapentin 300 mg in people with Neuropathic Pain and Type 2 Diabetes Mellitus, run by Natalia Valadares de Moraes.
Trial summary
This study aimed to investigate the influence of the glycemic control of type 2 diabetes (DM2) and of cetirizine (OCTs inhibitor) on gabapentin kinetics disposition and pharmacodynamics (PK-PD) in patients with neuropathic pain. Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- Neuropathic Pain, Type 2 Diabetes Mellitus, Diabetic Neuropathy, Painful
- What is being tested?
- Serial Blood Samples, Serial Urine Samples and Gabapentin 300 mg
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2015to 1 Jul 2019
- 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 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Adult patients, both gender
- Patients with neuropathic pain with score ≥ 4 in visual analog scale
- Patients with controlled type 2 diabetes (glycated hemoglobin ≤ 8.0%) and diabetic neuropathy with score ≥ 4 in visual analog scale
- Patients with uncontrolled type 2 diabetes (glycated hemoglobin ≥ 8.0%) and diabetic neuropathy with score ≥ 4 in visual analog scale
- Patients that suspend the use of analgesics for 10 times half-life before starting the protocol
Who cannot join
- Patients with acute or chronicle severe renal failure (creatinine clearance ≤ 30 mL/min)
- Patients with gastrointestinal diseases
- Patients with history of alcohol and drug abuse
- Patients with acute myocardial insufficiency
- Patients with another kind of chronicle pain as severe as neuropathic pain
- Patients in chronicle use of drugs that interact with gabapentin (antacids and cimetidine)
About this study
Official title: Gabapentin Kinetic Disposition and Renal Excretion: Role of Transporters for Organic Cations and the Effect of Glycemic Control in Patients With Neuropathic Pain.
This study aimed to investigate the influence of the glycemic control of type 2 diabetes (DM2) and of cetirizine (OCTs inhibitor) on gabapentin kinetics disposition and pharmacodynamics (PK-PD) in patients with neuropathic pain. Thus, non-diabetic patients (Control Group, n=10), patients with controlled diabetes (n=9) and patients with uncontrolled diabetes (n=10), all with neuropathic pain of intensity ≥ 4 in pain visual analog scale (0-10) were investigated.
Read the detailed description
Gabapentin (GBP), anticonvulsant used to neuropathic pain treatment, is mainly eliminated unchanged in urine. Renal active tubular secretion has been suggested to contribute on GBP excretion by renal excretion. Studies performed on rats with experimental diabetes suggest that hyperglycemia reduces the activity of organic cation transporters (Oct). Thus, the aim of the study was to investigate the role of OCTs on kinetic disposition and pharmacodynamics of GBP in patients with neuropathic pain and to verify the regulation of these transporters' activity by glycemic control in diabetes. A cross-over clinical study was performed in patients with neuropathic pain (n=10, Control) to evaluate the influence of CTZ on GBP kinetic disposition. To evaluate the effect of glycemic control, patients with controlled DM2 (DC, n=9) and uncontrolled DM2 (DNC, n=10) were investigated. All participants investigated had neuropathic pain of intensity ≥ 4 evaluated by analogue visual scale (EVA) and were treated with oral single-dose of 300 mg of GBP (Phase 1) or cetirizine (20 mg/day) for 5 days and single-dose of GBP on the last day (Phase 2). Only participants of Control group participated of Phase 2. Serial blood and urine samples were collected up to 36 hours after GBP administration. The intensity of pain was evaluated at the same time of blood sampling, using the visual analog scale. GBP concentration in plasma and urine was validated by JPLC-UV. All participants were genotyped for polymorphisms SLC22A2 808G>T and SLC22A4 1507C>T. The pharmacokinetic parameters were estimated by non-compartmental analysis.
- Being tested
- Serial Blood Samples, Serial Urine Samples, Gabapentin 300 mg, Cetirizine Hydrochloride 10 mg
- Medical subject headings
- Neuralgia, Diabetes Mellitus, Type 2, Diabetic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Serial Blood SamplesProcedure or surgery
Serial blood samples were collected at times 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 36 hours after gabapentin administration, for all patients.
Serial Urine SamplesProcedure or surgery
Serial urine samples were collected at intervals 0-8 hours, 8-16 hours, 16-24 hours and 24-36 hours after gabapentin administration, for all patients.
Gabapentin 300 mgDrug
All patients were treated with oral single dose of gabapentin 300 mg.
Cetirizine Hydrochloride 10 mgDrug
Patients of control group were treated with cetirizine hydrochloride, 10 mg, twice as day, orally, for five days.
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Active comparator | Adult patients (18 - 59 years old) with neuropathic pain of score ≥ 4 that do not use gabapentin were recruited. All patients received oral single dose of gabapentin (300 mg) as capsules after 12 hour-fasting (phase I). To investigate GBP pharmacokinetics, blood samples were collected in heparinized tubes up to 36 hours after GBP administration. The urine of the patients was collected up to 36 hours after GBP administration. The intensity of pain was evaluated in each time of blood sampling through the visual analog scale (0-10). In phase II, after 15 days (wash-out) from phase I, cetirizine hydrochloride (10 mg) was administered orally, twice a day, as pills, for five days. On the last day of cetirizine treatment, an oral single dose of gabapentin (300 mg), as capsule, was administered. Serial blood and urine samples were collected up to 36 hours after GBP administration. The intensity of pain was evaluated in each time of blood sampling. Receives: Procedure: Serial Blood Samples; Procedure: Serial Urine Samples; Drug: Gabapentin 300 mg; Drug: Cetirizine Hydrochloride 10 mg |
| Controlled Diabetes Group | Experimental | Adult patients (18 - 59 years old) with controlled type 2 diabetes (glycated hemoglobin ≤ 8.0%) and diabetic neuropathy of score ≥ 4 that do not use gabapentin were recruited. All patients received oral single dose of gabapentin (300 mg) as capsules after 12 hour-fasting. To investigate GBP pharmacokinetics, blood samples were collected in heparinized tubes up to 36 hours after GBP administration. The urine of the patients was collected up to 36 hours after GBP administration. The intensity of pain was evaluated in each time of blood sampling through the visual analog scale (0-10). Receives: Procedure: Serial Blood Samples; Procedure: Serial Urine Samples; Drug: Gabapentin 300 mg |
| Uncontrolled Diabetes Group | Experimental | Adult patients (18 - 59 years old) with uncontrolled type 2 diabetes (glycated hemoglobin ≥ 8.0%) and diabetic neuropathy of score ≥ 4 that do not use gabapentin were recruited. All patients received oral single dose of gabapentin (300 mg) as capsules after 12 hour-fasting. To investigate GBP pharmacokinetics, blood samples were collected in heparinized tubes up to 36 hours after GBP administration. The urine of the patients was collected up to 36 hours after GBP administration. The intensity of pain was evaluated in each time of blood sampling through the visual analog scale (0-10). Receives: Procedure: Serial Blood Samples; Procedure: Serial Urine Samples; Drug: Gabapentin 300 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic parameter (AUC)
Area under the plasma concentration versus time (AUC)
Measured: Up to 36 hours after gabapentin (300 mg) administration
Secondary outcomes (4)
Pharmacokinetic parameter (Total clearance)
Total clearance
Measured: Up to 36 hours after gabapentin (300 mg) administration
Pharmacokinetic parameter (Renal clearance)
Renal clearance
Measured: Up to 36 hours after gabapentin (300 mg) administration
Pharmacokinetic parameter (Vd)
Volume of distribution (Vd)
Measured: Up to 36 hours after gabapentin (300 mg) administration
Pharmacokinetic parameter (Elimination half-life)
Elimination half-life
Measured: Up to 36 hours after gabapentin (300 mg) administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2017 (estimated)
- Study start1 Nov 2015
- Primary completion1 May 2018
- Study completion1 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuropathic 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Natalia Valadares de Moraes
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sao Paulo
- Responsible party
- Sponsor-investigator, Natalia Valadares de Moraes, Universidade Estadual Paulista Júlio de Mesquita Filho
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03047278
- Sponsor's protocol ID
- GBPDIABETCET
- Status last verified
- Jul 2019
- First submitted
- 2 Feb 2017
- Last updated
- 5 Jul 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gabapentin Kinetic Disposition and Renal Excretion: Role of Transporters for Organic Cations and the Effect of Glycemic Control in Patients With Neuropathic Pain.
- ClinicalTrials.gov ID
- NCT03047278
- Acronym / sponsor ID
- GBPDIABETCET
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Natalia Valadares de MoraesUniversity, hospital or other
- Collaborators
- University of Sao Paulo
- Study start
- 1 Nov 2015 (actual)
- Primary completion
- 1 May 2018 (actual)
- Study completion
- 1 Jul 2019 (actual)
- First posted
- 8 Feb 2017 (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 aimed to investigate the influence of the glycemic control of type 2 diabetes (DM2) and of cetirizine (OCTs inhibitor) on gabapentin kinetics disposition and pharmacodynamics (PK-PD) in patients with neuropathic pain. Thus, non-diabetic patients (Control Group, n=10), patients with controlled diabetes (n=9) and patients with uncontrolled diabetes (n=10), all with neuropathic pain of intensity ≥ 4 in pain visual analog scale (0-10) were investigated.
Detailed description
Gabapentin (GBP), anticonvulsant used to neuropathic pain treatment, is mainly eliminated unchanged in urine. Renal active tubular secretion has been suggested to contribute on GBP excretion by renal excretion. Studies performed on rats with experimental diabetes suggest that hyperglycemia reduces the activity of organic cation transporters (Oct). Thus, the aim of the study was to investigate the role of OCTs on kinetic disposition and pharmacodynamics of GBP in patients with neuropathic pain and to verify the regulation of these transporters' activity by glycemic control in diabetes. A cross-over clinical study was performed in patients with neuropathic pain (n=10, Control) to evaluate the influence of CTZ on GBP kinetic disposition. To evaluate the effect of glycemic control, patients with controlled DM2 (DC, n=9) and uncontrolled DM2 (DNC, n=10) were investigated. All participants investigated had neuropathic pain of intensity ≥ 4 evaluated by analogue visual scale (EVA) and were treated with oral single-dose of 300 mg of GBP (Phase 1) or cetirizine (20 mg/day) for 5 days and single-dose of GBP on the last day (Phase 2). Only participants of Control group participated of Phase 2. Serial blood and urine samples were collected up to 36 hours after GBP administration. The intensity of pain was evaluated at the same time of blood sampling, using the visual analog scale. GBP concentration in plasma and urine was validated by JPLC-UV. All participants were genotyped for polymorphisms SLC22A2 808G>T and SLC22A4 1507C>T. The pharmacokinetic parameters were estimated by non-compartmental analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control Group | Active comparator | Procedure: Serial Blood Samples, Procedure: Serial Urine Samples, Drug: Gabapentin 300 mg, Drug: Cetirizine Hydrochloride 10 mgAdult patients (18 - 59 years old) with neuropathic pain of score ≥ 4 that do not use gabapentin were recruited. All patients received oral single dose of gabapentin (300 mg) as capsules after 12 hour-fasting (phase I). To investigate GBP pharmacokinetics, blood samples were collected in heparinized tubes up to 36 hours after GBP administration. The urine of the patients was collected up to 36 hours after GBP administration. The intensity of pain was evaluated in each time of blood sampling through the visual analog scale (0-10). In phase II, after 15 days (wash-out) from phase I, cetirizine hydrochloride (10 mg) was administered orally, twice a day, as pills, for five days. On the last day of cetirizine treatment, an oral single dose of gabapentin (300 mg), as capsule, was administered. Serial blood and urine samples were collected up to 36 hours after GBP administration. The intensity of pain was evaluated in each time of blood sampling. |
| Controlled Diabetes Group | Experimental | Procedure: Serial Blood Samples, Procedure: Serial Urine Samples, Drug: Gabapentin 300 mgAdult patients (18 - 59 years old) with controlled type 2 diabetes (glycated hemoglobin ≤ 8.0%) and diabetic neuropathy of score ≥ 4 that do not use gabapentin were recruited. All patients received oral single dose of gabapentin (300 mg) as capsules after 12 hour-fasting. To investigate GBP pharmacokinetics, blood samples were collected in heparinized tubes up to 36 hours after GBP administration. The urine of the patients was collected up to 36 hours after GBP administration. The intensity of pain was evaluated in each time of blood sampling through the visual analog scale (0-10). |
| Uncontrolled Diabetes Group | Experimental | Procedure: Serial Blood Samples, Procedure: Serial Urine Samples, Drug: Gabapentin 300 mgAdult patients (18 - 59 years old) with uncontrolled type 2 diabetes (glycated hemoglobin ≥ 8.0%) and diabetic neuropathy of score ≥ 4 that do not use gabapentin were recruited. All patients received oral single dose of gabapentin (300 mg) as capsules after 12 hour-fasting. To investigate GBP pharmacokinetics, blood samples were collected in heparinized tubes up to 36 hours after GBP administration. The urine of the patients was collected up to 36 hours after GBP administration. The intensity of pain was evaluated in each time of blood sampling through the visual analog scale (0-10). |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Adult patients, both gender
- Patients with neuropathic pain with score ≥ 4 in visual analog scale
- Patients with controlled type 2 diabetes (glycated hemoglobin ≤ 8.0%) and diabetic neuropathy with score ≥ 4 in visual analog scale
- Patients with uncontrolled type 2 diabetes (glycated hemoglobin ≥ 8.0%) and diabetic neuropathy with score ≥ 4 in visual analog scale
- Patients that suspend the use of analgesics for 10 times half-life before starting the protocol
Key exclusion criteria (6 listed)
- Patients with acute or chronicle severe renal failure (creatinine clearance ≤ 30 mL/min)
- Patients with gastrointestinal diseases
- Patients with history of alcohol and drug abuse
- Patients with acute myocardial insufficiency
- Patients with another kind of chronicle pain as severe as neuropathic pain
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 |
|---|---|---|
| Serial Blood SamplesSerial blood samples were collected at times 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 36 hours after gabapentin administration, for all patients. | Procedure or surgery | Control Group, Controlled Diabetes Group, Uncontrolled Diabetes Group |
| Serial Urine SamplesSerial urine samples were collected at intervals 0-8 hours, 8-16 hours, 16-24 hours and 24-36 hours after gabapentin administration, for all patients. | Procedure or surgery | Control Group, Controlled Diabetes Group, Uncontrolled Diabetes Group |
| Gabapentin 300 mgAll patients were treated with oral single dose of gabapentin 300 mg. | Drug | Control Group, Controlled Diabetes Group, Uncontrolled Diabetes Group |
| Cetirizine Hydrochloride 10 mgPatients of control group were treated with cetirizine hydrochloride, 10 mg, twice as day, orally, for five days. | Drug | Control Group |
Primary outcome
Pharmacokinetic parameter (AUC)
Time frame: Up to 36 hours after gabapentin (300 mg) administration
Area under the plasma concentration versus time (AUC)
4 secondary outcomes
Pharmacokinetic parameter (Total clearance)
Time frame: Up to 36 hours after gabapentin (300 mg) administration
Pharmacokinetic parameter (Renal clearance)
Time frame: Up to 36 hours after gabapentin (300 mg) administration
Pharmacokinetic parameter (Vd)
Time frame: Up to 36 hours after gabapentin (300 mg) administration
Pharmacokinetic parameter (Elimination half-life)
Time frame: Up to 36 hours after gabapentin (300 mg) administration
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 5 Jul 2019.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Serial Blood Samples, Serial Urine Samples and Gabapentin 300 mg in people with Neuropathic Pain and Type 2 Diabetes Mellitus, run by Natalia Valadares de Moraes.
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 6 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 5 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
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 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?
Pharmacokinetic parameter (AUC) (time frame: Up to 36 hours after gabapentin (300 mg) administration). 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 5 Jul 2019.