Chronic Granulomatous DiseasePhase 1/2NCT03080480
Pioglitazone Therapy for Chronic Granulomatous Disease
A Phase 1/2 study testing Pioglitazone in people with Chronic Granulomatous Disease, run by Children's Hospital of Fudan University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 month to 18 years
- Conditions the study is for
- Chronic Granulomatous Disease
- What is being tested?
- Pioglitazone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2017to 20 Oct 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age：1 months to 18 years
- Chronic Granulomatous Disease
- with severe infections
Who cannot join
- > 18 years of age
- infections are treatable by conventional therapy (antibiotics, antimycotics, allogeneic granulocytes)
Trial locations and contacts
1 site in 1 country.
China1 site
Children's Hospital of Fudan University
Shanghai, Shanghai Municipality, 201102
About this study
Official title: 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.
Read the 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.
- Conditions
- Chronic Granulomatous Disease
- Being tested
- Pioglitazone
- Keywords
- Chronic Granulomatous Disease, Severe Infection, PPARγ, Pioglitazone, phagocytes
- Medical subject headings
- Granulomatous Disease, Chronic, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called ACTOS
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.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone | Experimental | Treatment for chronic granulomatous disease patients with severe infection. Receives: Drug: Pioglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
efficiency of Pioglitazone
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).
Measured: 3 years
Secondary outcomes (1)
Incidence of Treatment-Emergent Adverse Events
Frequency and severity of metabolic disorders and unexpected toxic adverse events during and after using pioglitazone
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2017
- Study start1 Sep 2017
- Primary completion20 Oct 2019
- Study completion20 Oct 2019
Why it stopped: The results are negtive.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Granulomatous DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital of Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jinqiao Sun, Children's Hospital of Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03080480
- Sponsor's protocol ID
- PTSICGD
- Status last verified
- Oct 2019
- First submitted
- 27 Feb 2017
- Last updated
- 22 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Migliavacca M, Assanelli A, Ferrua F, Cicalese MP, Biffi A, Frittoli M, Silvani P, Chidini G, Calderini E, Mandelli A, Camporesi A, Milani R, Farinelli G, Nicoletti R, Ciceri F, Aiuti A, Bernardo ME. Pioglitazone as a novel therapeutic approach in chronic granulomatous disease. J Allergy Clin Immunol. 2016 Jun;137(6):1913-1915.e2. doi: 10.1016/j.jaci.2016.01.033. Epub 2016 Apr 4. No abstract available.
PubMed 27056268Fernandez-Boyanapalli RF, Falcone EL, Zerbe CS, Marciano BE, Frasch SC, Henson PM, Holland SM, Bratton DL. Impaired efferocytosis in human chronic granulomatous disease is reversed by pioglitazone treatment. J Allergy Clin Immunol. 2015 Nov;136(5):1399-1401.e3. doi: 10.1016/j.jaci.2015.07.034. Epub 2015 Sep 18. No abstract available.
PubMed 26386811Fernandez-Boyanapalli RF, Frasch SC, Thomas SM, Malcolm KC, Nicks M, Harbeck RJ, Jakubzick CV, Nemenoff R, Henson PM, Holland SM, Bratton DL. Pioglitazone restores phagocyte mitochondrial oxidants and bactericidal capacity in chronic granulomatous disease. J Allergy Clin Immunol. 2015 Feb;135(2):517-527.e12. doi: 10.1016/j.jaci.2014.10.034. Epub 2014 Dec 10.
PubMed 25498313Hui X, Liu D, Wang W, Hou J, Ying W, Zhou Q, Yao H, Sun J, Wang X. Low-Dose Pioglitazone does not Increase ROS Production in Chronic Granulomatous Disease Patients with Severe Infection. J Clin Immunol. 2020 Jan;40(1):131-137. doi: 10.1007/s10875-019-00719-z. Epub 2019 Nov 19.
PubMed 31745699
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Pioglitazone Therapy for Chronic Granulomatous Disease Patients With Severe Infection.
- ClinicalTrials.gov ID
- NCT03080480
- Acronym / sponsor ID
- PTSICGD
- Conditions
- Chronic Granulomatous Disease
- Keywords
- Chronic Granulomatous Disease, Severe Infection, PPARγ, Pioglitazone, phagocytes
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The results are negtive.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Children's Hospital of Fudan UniversityUniversity, hospital or other
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 20 Oct 2019 (actual)
- Study completion
- 20 Oct 2019 (actual)
- First posted
- 15 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Experimental | Drug: PioglitazoneTreatment for chronic granulomatous disease patients with severe infection. |
Who may qualify
- Ages
- 1 month to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Age：1 months to 18 years
- Chronic Granulomatous Disease
- with severe infections
Key exclusion criteria (2 listed)
- > 18 years of age
- infections are treatable by conventional therapy (antibiotics, antimycotics, allogeneic granulocytes)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PioglitazoneAlso: ACTOSPioglitazone 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. | Drug | Pioglitazone |
Primary outcome
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).
1 secondary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: 3 years
Results and safety
The study was stopped early (reason given: The results are negtive.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2019.
- Background: PubMed 27056268Migliavacca M, Assanelli A, Ferrua F, Cicalese MP, Biffi A, Frittoli M, Silvani P, Chidini G, Calderini E, Mandelli A, Camporesi A, Milani R, Farinelli G, Nicoletti R, Ciceri F, Aiuti A, Bernardo ME. Pioglitazone as a novel therapeutic approach in chronic granulomatous disease. J Allergy Clin Immunol. 2016 Jun;137(6):1913-1915.e2. doi: 10.1016/j.jaci.2016.01.033. Epub 2016 Apr 4. No abstract available.
- Background: PubMed 26386811Fernandez-Boyanapalli RF, Falcone EL, Zerbe CS, Marciano BE, Frasch SC, Henson PM, Holland SM, Bratton DL. Impaired efferocytosis in human chronic granulomatous disease is reversed by pioglitazone treatment. J Allergy Clin Immunol. 2015 Nov;136(5):1399-1401.e3. doi: 10.1016/j.jaci.2015.07.034. Epub 2015 Sep 18. No abstract available.
- Background: PubMed 25498313Fernandez-Boyanapalli RF, Frasch SC, Thomas SM, Malcolm KC, Nicks M, Harbeck RJ, Jakubzick CV, Nemenoff R, Henson PM, Holland SM, Bratton DL. Pioglitazone restores phagocyte mitochondrial oxidants and bactericidal capacity in chronic granulomatous disease. J Allergy Clin Immunol. 2015 Feb;135(2):517-527.e12. doi: 10.1016/j.jaci.2014.10.034. Epub 2014 Dec 10.
- Derived from this study: PubMed 31745699Hui X, Liu D, Wang W, Hou J, Ying W, Zhou Q, Yao H, Sun J, Wang X. Low-Dose Pioglitazone does not Increase ROS Production in Chronic Granulomatous Disease Patients with Severe Infection. J Clin Immunol. 2020 Jan;40(1):131-137. doi: 10.1007/s10875-019-00719-z. Epub 2019 Nov 19.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pioglitazone in people with Chronic Granulomatous Disease, run by Children's Hospital of Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The results are negtive.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
efficiency of Pioglitazone (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03080480, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2019.