Trial record 3 of 26 for:    Recruiting, Not yet recruiting, Available Studies | "Granulomatous Disease, Chronic"

Pioglitazone Therapy for Chronic Granulomatous Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03080480
Recruitment Status : Recruiting
First Posted : March 15, 2017
Last Update Posted : December 6, 2018
Information provided by (Responsible Party):
Jinqiao Sun, Children's Hospital of Fudan University

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
Chronic Granulomatous Disease Drug: Pioglitazone 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
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 : September 1, 2017
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : August 31, 2020

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 Name: ACTOS

Primary Outcome Measures :
  1. 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).

Secondary Outcome Measures :
  1. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 18 Years   (Child, Adult)
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03080480

Contact: Jinqiao Sun, Ph.D.,M.D 86-21-64932909
Contact: Weili Yan, Ph.D. 86-21-64931913

China, Shanghai
Children's Hospital of Fudan University Recruiting
Shanghai, Shanghai, China, 201102
Contact: Weili Yan, Ph.D   
Sponsors and Collaborators
Children's Hospital of Fudan University

Responsible Party: Jinqiao Sun, Professor, Children's Hospital of Fudan University Identifier: NCT03080480     History of Changes
Other Study ID Numbers: PTSICGD
First Posted: March 15, 2017    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
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, Children's Hospital of Fudan University:
Chronic Granulomatous Disease
Severe Infection

Additional relevant MeSH terms:
Granulomatous Disease, Chronic
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs