Clincosm LogoSign in Get a demo

Pioglitazone Therapy for Chronic Granulomatous Disease

Sponsor
Children's Hospital of Fudan University (Other)
Overall Status
Terminated
CT.gov ID
NCT03080480
Collaborator
(none)
3
Enrollment
1
Location
1
Arm
25.6
Actual Duration (Months)
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
3 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Efficacy and Safety of Pioglitazone Therapy for Chronic Granulomatous Disease Patients With Severe Infection.
Actual Study Start Date :
Sep 1, 2017
Actual Primary Completion Date :
Oct 20, 2019
Actual Study Completion Date :
Oct 20, 2019

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. efficiency of Pioglitazone [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).

    Secondary Outcome Measures

    1. Incidence of Treatment-Emergent Adverse Events [3 years]

      Frequency and severity of metabolic disorders and unexpected toxic adverse events during and after using pioglitazone

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Month to 18 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Fudan University Shanghai Shanghai China 201102

    Sponsors and Collaborators

    • Children's Hospital of Fudan University

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Jinqiao Sun, Professor, Children's Hospital of Fudan University
    ClinicalTrials.gov Identifier:
    NCT03080480
    Other Study ID Numbers:
    • PTSICGD
    First Posted:
    Mar 15, 2017
    Last Update Posted:
    Oct 22, 2019
    Last Verified:
    Oct 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Jinqiao Sun, Professor, Children's Hospital of Fudan University
    Chronic Granulomatous Disease
    Severe Infection
    PPARγ
    Pioglitazone
    phagocytes
    Additional relevant MeSH terms:
    Granuloma
    Granulomatous Disease, Chronic
    Pioglitazone

    Study Results

    No Results Posted as of Oct 22, 2019