- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03047278
Transporters for Organic Cations and Glycemic Control in Patients With Neuropathic Pain.
July 1, 2019 updated by: Natalia Valadares de Moraes
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.
Study Overview
Status
Completed
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 Type
Interventional
Enrollment (Actual)
29
Phase
- Phase 4
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 59 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Control Group
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.
|
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 samples were collected at intervals 0-8 hours, 8-16 hours, 16-24 hours and 24-36 hours after gabapentin administration, for all patients.
All patients were treated with oral single dose of gabapentin 300 mg.
Patients of control group were treated with cetirizine hydrochloride, 10 mg, twice as day, orally, for five days.
|
Experimental: Controlled Diabetes Group
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).
|
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 samples were collected at intervals 0-8 hours, 8-16 hours, 16-24 hours and 24-36 hours after gabapentin administration, for all patients.
All patients were treated with oral single dose of gabapentin 300 mg.
|
Experimental: Uncontrolled Diabetes Group
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).
|
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 samples were collected at intervals 0-8 hours, 8-16 hours, 16-24 hours and 24-36 hours after gabapentin administration, for all patients.
All patients were treated with oral single dose of gabapentin 300 mg.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetic parameter (AUC)
Time Frame: Up to 36 hours after gabapentin (300 mg) administration
|
Area under the plasma concentration versus time (AUC)
|
Up to 36 hours after gabapentin (300 mg) administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetic parameter (Total clearance)
Time Frame: Up to 36 hours after gabapentin (300 mg) administration
|
Total clearance
|
Up to 36 hours after gabapentin (300 mg) administration
|
Pharmacokinetic parameter (Renal clearance)
Time Frame: Up to 36 hours after gabapentin (300 mg) administration
|
Renal clearance
|
Up to 36 hours after gabapentin (300 mg) administration
|
Pharmacokinetic parameter (Vd)
Time Frame: Up to 36 hours after gabapentin (300 mg) administration
|
Volume of distribution (Vd)
|
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
|
Elimination half-life
|
Up to 36 hours after gabapentin (300 mg) administration
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 1, 2015
Primary Completion (Actual)
May 1, 2018
Study Completion (Actual)
July 1, 2019
Study Registration Dates
First Submitted
February 2, 2017
First Submitted That Met QC Criteria
February 7, 2017
First Posted (Estimate)
February 8, 2017
Study Record Updates
Last Update Posted (Actual)
July 5, 2019
Last Update Submitted That Met QC Criteria
July 1, 2019
Last Verified
July 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Nervous System Diseases
- Pain
- Neurologic Manifestations
- Endocrine System Diseases
- Diabetes Complications
- Diabetes Mellitus
- Neuromuscular Diseases
- Peripheral Nervous System Diseases
- Diabetes Mellitus, Type 2
- Neuralgia
- Diabetic Neuropathies
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Anti-Anxiety Agents
- Anticonvulsants
- Antimanic Agents
- Anti-Allergic Agents
- Histamine H1 Antagonists
- Histamine Antagonists
- Histamine Agents
- Histamine H1 Antagonists, Non-Sedating
- Gabapentin
- Cetirizine
Other Study ID Numbers
- GBPDIABETCET
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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