Transporters for Organic Cations and Glycemic Control in Patients With Neuropathic Pain.

Type 2 Diabetes Mellitus Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03047278
• Other study ID #: GBPDIABETCET
• Status: Completed
• Phase: Phase 4
• Start date: November 1, 2015
• Est. completion date: July 1, 2019

Study information

• Verified date: July 2019
• Source: Universidade Estadual Paulista Júlio de Mesquita Filho
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: July 1, 2019
• Est. primary completion date: May 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetic Neuropathies
• Diabetic Neuropathy, Painful
• Neuralgia
• Neuropathic Pain
• Type 2 Diabetes Mellitus

Intervention

Procedure:
• Serial Blood Samples
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
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.

Drug:
• Gabapentin 300 mg
All patients were treated with oral single dose of gabapentin 300 mg.
• Cetirizine Hydrochloride 10 mg
Patients of control group were treated with cetirizine hydrochloride, 10 mg, twice as day, orally, for five days.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Natalia Valadares de Moraes	University of Sao Paulo

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic parameter (AUC)	Area under the plasma concentration versus time (AUC)	Up to 36 hours after gabapentin (300 mg) administration
Secondary	Pharmacokinetic parameter (Total clearance)	Total clearance	Up to 36 hours after gabapentin (300 mg) administration
Secondary	Pharmacokinetic parameter (Renal clearance)	Renal clearance	Up to 36 hours after gabapentin (300 mg) administration
Secondary	Pharmacokinetic parameter (Vd)	Volume of distribution (Vd)	Up to 36 hours after gabapentin (300 mg) administration
Secondary	Pharmacokinetic parameter (Elimination half-life)	Elimination half-life	Up to 36 hours after gabapentin (300 mg) administration