Epithelial Sodium Channel (ENaC) as a Novel Mechanism for Hypertension and Volume Expansion in Type 2 Diabetes

NCT01804777 | Terminated Early Phase 1 DMC

• 1 other identifier: 13-017
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine with the administration of amiloride, observe an enhanced natriuresis, reduction in blood pressure and weight compared to the administration of hydrochlorothiazide in Type 2 Diabetics.

Conditions

Proteinuria; Hypertension; Type II Diabetes

Keywords

ENaC; Amiloride; Hydrochlorothiazide(HCTZ); Hypertension; Type II Diabetes; Natriuresis; Proteinuria

Outcome Measures

Primary Outcomes (1)

• Blood Pressure

  Change in clinic systolic BP. This BP measure will be the average of three serial BP measurements taken one minute apart after 5 minutes of sitting quietly.

  one month

Secondary Outcomes (1)

• Hypertension

  one month

Study Arms (2)

Amiloride 10 mg, 20 mg, and diet

EXPERIMENTAL

Amiloride 10 mg for 14 days and diet. Then dose titrated up at day 14 to 20 mg, and diet.

Drug: Amiloride

HCTZ 12.5 mg, 25 mg and diet

ACTIVE COMPARATOR

HCTZ 12.5 mg for 14 days and diet. Then dose titrated up at day 14 to 25 mg, and diet

Drug: HCTZ

Interventions

Amiloride DRUG

Amiloride 10 mg taken every day for two weeks, along with adherence to specified diet. On day 14 titrate dose up to Amiloride 20 mg, take every day for two weeks after completion of two week intake of Amiloride 10 mg, along with adherence to specified diet.

Also known as: Midamor

Amiloride 10 mg, 20 mg, and diet

HCTZ DRUG

HCTZ 12.5 mg taken every day for two weeks, along with adherence to specified diet. On day 14 titrate dose up to HCTZ 25 mg taken every day for two weeks after completion of two week intake of HCTZ 12.5 mg, along with adherence to specified diet

Also known as: Hydrochlorthiazide, Aquazide H, HydroDIURIL, Microzide

HCTZ 12.5 mg, 25 mg and diet

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 80 yrs at randomization
• History of Type 2 Diabetes
• Presence of systolic hypertension or pre-hypertension (average systolic blood pressure (SBP) ≥120 mmHg and \<180 mmHg.)
• Urinary protein/creatinine ratio \>300 mg/g creatinine at screening
• Hemoglobin A1C\<8%
• Willing and able to give informed consent

You may not qualify if:

• Average SBP of ≥180 mmHg or diastolic blood pressure (DBP) of ≥110 mmHg
• Current symptomatic heart failure, history of New York Heart Association Class III or IV congestive heart failure, or left ventricular (LV) ejection fraction (by any method) \<25%; these patients may be harmed with withdrawal of diuretics
• Serum potassium level \<3.5 or \>5.0 at screening
• History of hyperkalemia in the last two years (serum K\>5.5)
• Contraindication to use of hydrochlorothiazide or amiloride
• Unstable angina pectoris or acute myocardial infarction (MI) in last 3 months
• Known secondary causes of hypertension (HTN) (screening for these conditions will not be required)
• Estimated glomerular filtration rate (GFR) \<60 mL/min/1.73m², as determined by validated estimating equations
• On or expected to be on immunosuppressive therapy
• Any history of solid organ transplantation
• Significant dementia
• Other factors likely to limit adherence during trial (eg. alcohol or substance abuse, plan to move in next year, history of non-adherence to medications, appointments and medical care, reluctance of close family members to participate in trial, lack of support from primary healthcare provider)
• Participation in another investigational trial within 4 weeks of the screening visit
• Arm Circumference too large or too small to allow accurate blood pressure measurement
• Pregnancy or currently trying to become pregnant (although this is unlikely because of age limit

Sponsors & Collaborators

• University of New Mexico: lead
• Dialysis Clinic, Inc.: collaborator
• University of Pittsburgh: collaborator

Study Sites (1)

University of New Mexico Hospital; Clinical & Translational Science Center

Albuquerque, New Mexico, 87131, United States

Location

Related Publications (1)

• Passero CJ, Hughey RP, Kleyman TR. New role for plasmin in sodium homeostasis. Curr Opin Nephrol Hypertens. 2010 Jan;19(1):13-9. doi: 10.1097/MNH.0b013e3283330fb2.

  PMID: 19864949 BACKGROUND

MeSH Terms

Conditions

Proteinuria; Hypertension; Diabetes Mellitus, Type 2

Interventions

Amiloride; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mark L Unruh, MD MSc

  University of New Mexico

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2013
• First Posted: March 5, 2013
• Study Start: March 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 11, 2018

Record last verified: 2018-05

Locations

US (1)