Pioglitazone Therapy for Chronic Granulomatous Disease

October 19, 2019 updated by: Jinqiao Sun, Children's Hospital of Fudan University

Efficacy and Safety of Pioglitazone Therapy for Chronic Granulomatous Disease Patients With Severe Infection.

The purpose of this proposed research is to investigate the efficacy and safety of the therapy with pioglitazone for chronic granulomatous disease (CGD) patients severe infection.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Chronic granulomatous disease (CGD) is a rare genetic disease caused by defects in genes encoding the subunits of the nicotinamide adenine dinucleotide（NADPH）phosphate oxidase complex. In normal phagocytes peroxisome proliferator-activated receptor gamma (PPARγ) activation links NADPH oxidase activity with enhanced mitochondrial reactive oxygen species (ROS) production. There is deficient mitochondrial ROS production in CGD，due to the lack of this upstream signaling by the NADPH oxidase and PPARγ. These patients are susceptible to bacterial and fungal infections, as well as extensive tissue granuloma formation. X-chromosome-linked CGD (X-CGD) is most frequently. And it generally produces a severe phenotype, with a mortality rate of 3% to 5% per year despite state-of-the-art prophylaxis and intensive multimodal treatment.

At present the most curative treatment for patients with X-CGD is hematopoietic stem cell transplantion (HSCT). But for many patients without an HLA-matched donor and active infections/inflammatory complications still require novel approches.

PPARγ agonist such as pioglitazone, approved for type 2 diabetes, was reported to bypass the need for the NADPH oxidase for enhanced mtROS production and partially restored host defense in CGD. What's more, some animal models and several clinical cases have proved its efficacy. The investigators propose to study the efficacy and safety of the therapy with pioglitazone for children with severe infection of CGD, and its long-term effects.

Through this study the investigators hope to confirm the benefits of pioglitazone in the treatment of this rare disease especially for those patients without a prompt suitable matched donor or for whom the critical disease conditions force to postpone HSCT.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 201102
        • Children's Hospital of Fudan University

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

1 year to 16 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age：1 months to 18 years
  2. Chronic Granulomatous Disease
  3. with severe infections

Exclusion Criteria:

  1. > 18 years of age
  2. infections are treatable by conventional therapy (antibiotics, antimycotics, allogeneic granulocytes)

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pioglitazone
Treatment for chronic granulomatous disease patients with severe infection.
Drug: Pioglitazone

Pioglitazone is PPARγ agonist that may be enhance ROS production and partially restore host phagocytes in CGD.

pioglitazone is administered at a starting dose of 1 mg/kg and given the absence of adverse effects is progressively increased up to 3 mg/kg or 30 mg/daily.

Other Names:
  • ACTOS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
efficiency of Pioglitazone
Time Frame: 3 years
Frequency of infections as indicator for the drug's benefit for the patients; Functional reconstitution of the NADPH oxidase in circulating cells of the peripheral blood (Stimulation Index by DHR analysis).
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Events
Time Frame: 3 years
Frequency and severity of metabolic disorders and unexpected toxic adverse events during and after using pioglitazone
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

September 1, 2017

Primary Completion (Actual)

October 20, 2019

Study Completion (Actual)

October 20, 2019

Study Registration Dates

First Submitted

February 27, 2017

First Submitted That Met QC Criteria

March 9, 2017

First Posted (Actual)

March 15, 2017

Study Record Updates

Last Update Posted (Actual)

October 22, 2019

Last Update Submitted That Met QC Criteria

October 19, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PTSICGD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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