Pioglitazone to Reduce Sympathetic Overactivity in CKD Patients

NCT03471117 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: CKD-IRB-2016-0005
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

Chronic kidney disease (CKD) is associated with a higher risk of cardiovascular disease and death. An overactive sympathetic nervous system in CKD patients is one of the major mechanisms increasing the cardiovascular risks in this patient population. Recently, some studies have shown that a drug typically used to improve glucose control (pioglitazone) may also reduce sympathetic nerve activity and improve blood vessel function. The goal of this study is to determine whether a short-term treatment with pioglitazone can reduce sympathetic nerve impulses throughout the body in CKD patients.

Conditions

Chronic Kidney Diseases

Keywords

blood pressure; pioglitazone; hypertension

Outcome Measures

Primary Outcomes (1)

• Muscle sympathetic nerve activity (MSNA) will be reduced after 1 month of treatment with pioglitazone

  Multiunit postganglionic MSNA will be recorded using standard microneurographic techniques. Briefly, a unipolar tungsten microelectrode will be inserted into the peroneal nerve near the fibular head of the leg. Neural signals will be amplified, filtered (bandwidth, 700-2,000 Hz), rectified, and integrated (time constant, 0.1 s) to obtain mean voltage neurograms.

  1 month

Study Arms (2)

Pioglitazone

ACTIVE COMPARATOR

The subjects will be given 1 month supply of Pioglitazone pills. Pioglitazone is a class of anti-diabetic drugs called thiazolidinediones that are primarily used in the treatment of type 2 diabetes. The aim of the study is to determine if Pioglitazone also reduces ADMA and sympathetic nerve activity in CKD patients. This drug will be taken orally as a pill or capsule for one month. The dosage is 15 mg/day. This is on the lower dosage side for pioglitazone with the maximum dosage being 45mg/day. The research subjects are not responsible for the cost of the drug or for drug administration costs. The subjects will be verbally instructed to take 1 pill everyday by mouth, for 1 month. In addition, the pill bottle will be labeled with the same instructions.

Drug: Pioglitazone

Placebo

PLACEBO COMPARATOR

Placebo pills are made of avicel microcrystalline cellulose and magnesium stearate, which are inactive ingredients in the Pioglitazone pills. The placebo pills will be of similar color and appearance as the Pioglitazone pills

Other: Placebo

Interventions

Pioglitazone DRUG

Pioglitazone 15mg daily for 1 month

Pioglitazone

Placebo OTHER

Placebo pills for 1 month

Placebo

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CKD patients classified as Stage 3 and 4 of National Kidney Foundation Classification with estimated glomerular filtration rate (GFR) between 15 and 59 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) formula based on serum creatinine, age, gender, and race.
• Men and women 35 to 70 years of age

You may not qualify if:

• Allergy to Glitazones
• Myocardial infarction
• Heart failure
• Angina
• History of kidney stones
• Liver disease (abnormal liver enzymes)
• Anemia (hemoglobin \<8 g/dl)
• Cancer with current treatment
• Previous organ transplantation
• Immunosuppressant therapy
• Human immunodeficiency virus infection
• Pregnancy or lactating
• Current tobacco use
• Dilantin and oral contraceptive usage due to potential drug interaction with glitazones
• Self-identified history of hypoglycemia

Sponsors & Collaborators

• The University of Texas at Arlington: lead
• University of Texas, Southwestern Medical Center at Dallas: collaborator

Study Sites (2)

University of Texas at Arlington

Arlington, Texas, 76010, United States

RECRUITING

UT Southwestern

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hypertension

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Paul J Fadel, PhD

  University of Texas at Arlington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul J Fadel, PhD

CONTACT

8172724653; Paul.Fadel@uta.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Subjects will either receive placebo or pioglitazone pills in a randomized order. Placebo pills will be sugar pills of same shape and size as the pioglitazone pills. The randomization for study drugs will be carried out by research personnel. All treatments will be encapsulated so that pills are identical and patients cannot identify the treatment arm.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This will be a randomized, placebo-controlled crossover design study

Study Record Dates

• First Submitted: February 12, 2018
• First Posted: March 20, 2018
• Study Start: April 1, 2018
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)