Effects of Pioglitazone in Calcific Aortic Valve Disease

NCT05875675 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: WUHFACAVD02
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, randomized, comparative, clinical trial conducted by Wuhan Union Hospital that aims to evaluate the efficacy and safety of pioglitazone compared to placebo in patients with calcific aortic valve disease with mild aortic valve stenosis.

Conditions

Calcification of Aortic Valve; Aortic Valve Stenosis

Keywords

Calcification of Aortic Valve; Aortic Valve Stenosis; Pioglitazone

Outcome Measures

Primary Outcomes (1)

• overall survival

  overall survival (OS)

  3 years

Secondary Outcomes (4)

• Time-to-major adverse cardiovascular events

  104 weeks

• Change in aortic valve stenosis severity

  at week 104

• HbA1c

  104 weeks

• Glucose level

  104 weeks

Study Arms (2)

Drug group

EXPERIMENTAL

Dietary Supplement: Pioglitazone 30 mg by mouth daily

Drug: Drug: Pioglitazone Oral Tablet

Control group

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Dietary Supplement: Placebo

Interventions

Drug: Pioglitazone Oral Tablet DRUG

Dietary Supplement: Pioglitazone 30 mg by mouth daily

Drug group

Placebo DIETARY_SUPPLEMENT

Dietary: Supplement: Placebo

Control group

Eligibility Criteria

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

You may qualify if:

• Male or female adult ≥ 35 years of age at the time of rescruiting.
• Subject has calcific aortic valve disease with mild to moderate aortic valve stenosis as defined by Doppler echocardiography results: Aortic Valve mean pressure gradient between 10-30 mmHg and Aortic Valve Area ≥ 1.2 and ≤ 2.0 cm2 on TTE within 2 weeks prior to randomization and Cardiac Compute Tomography (CT) test results: aortic valve calcium score (Agatston score) ≥ 200 AU at baseline cardiac CT within 1 month prior to randomization
• Subject provides written informed consent prior to initiation of any study procedures.
• Subject understands and agrees to comply with planned study procedures.

You may not qualify if:

• Subject has concomitant moderate or severe mitral or tricuspid valve disease.
• Subject has left ventricular ejection fraction \< 50%.
• Subject previous history of aortic valve surgery, pancreatitis, malignant tumor, drug or alcohol abuse.
• Subjects whose alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal range.
• Subjects who cannot undergo Cardiac CT.
• Pregnant or lactating women.
• Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Related Publications (4)

• Chu Y, Lund DD, Weiss RM, Brooks RM, Doshi H, Hajj GP, Sigmund CD, Heistad DD. Pioglitazone attenuates valvular calcification induced by hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):523-32. doi: 10.1161/ATVBAHA.112.300794. Epub 2013 Jan 3.

  PMID: 23288158 BACKGROUND

• Greenberg HZE, Zhao G, Shah AM, Zhang M. Role of oxidative stress in calcific aortic valve disease and its therapeutic implications. Cardiovasc Res. 2022 May 6;118(6):1433-1451. doi: 10.1093/cvr/cvab142.

  PMID: 33881501 BACKGROUND

• Hajj GP, Chu Y, Lund DD, Magida JA, Funk ND, Brooks RM, Baumbach GL, Zimmerman KA, Davis MK, El Accaoui RN, Hameed T, Doshi H, Chen B, Leinwand LA, Song LS, Heistad DD, Weiss RM. Spontaneous Aortic Regurgitation and Valvular Cardiomyopathy in Mice. Arterioscler Thromb Vasc Biol. 2015 Jul;35(7):1653-62. doi: 10.1161/ATVBAHA.115.305729. Epub 2015 May 21.

  PMID: 25997932 BACKGROUND

• Weiss RM, Miller JD, Heistad DD. Fibrocalcific aortic valve disease: opportunity to understand disease mechanisms using mouse models. Circ Res. 2013 Jul 5;113(2):209-22. doi: 10.1161/CIRCRESAHA.113.300153.

  PMID: 23833295 BACKGROUND

MeSH Terms

Conditions

Aortic Valve, Calcification of; Aortic Valve Stenosis

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Fei Li, MD

CONTACT

15972969897; lifei_union@hust.edu.cn

Li Xu

CONTACT

15387030212; unionxuli@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2023
• First Posted: May 25, 2023
• Study Start: July 1, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 25, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: All data should only be used for academic research.