Ignite Creation Date:
2024-05-05 @ 10:19 PM
Last Modification Date:
2024-10-26 @ 10:17 AM
Study NCT ID:
NCT01083524
Status:
COMPLETED
Last Update Posted:
2014-06-03
First Post:
2010-03-08
Brief Title:
Dichloroacetate DCA for the Treatment of Pulmonary Arterial Hypertension
Sponsor:
University of Alberta
Organization:
University of Alberta
Study Overview
Official Title:
A Phase I Open-Label Two Centre Study to Evaluate DichloroacetateDCA in Advanced Pulmonary Arterial Hypertension
Status:
COMPLETED
Status Verified Date:
2014-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Hypothesis The small molecule and metabolic modulator Dichloroacetate DCA is safe tolerated as a potential therapy in patients with moderate or severe Pulmonary Arterial Hypertension PAH
This is a Phase I two centre study in subjects with PAH WHO functional class III-IV whose symptoms have been clinically stable on their prescribed medical treatment which includes endothelin andor phosphodiesterase type 5 inhibitors for 8 weeks prior to enrollment Such patients will be given either DCA 30 mgkg BID group I 625 mgkg BID group II or 125 mgkg BID group III as an additional treatment for 16 weeks The design is open-label with the subjects acting as their own controls
Primary endpoint is the safety and tolerability of DCA Secondary end points include a functional capacity including a change in the 6 minute walk form baseline b change in pulmonary vascular resistance measured by right heart catheterization c right ventricular volumes and mass measured by MRI d NT-proBNP levels changed from baseline e change in FDG-glucose uptake in the lung and right ventricle measured by PET and f change in quality of life indices
15 evaluable patients in each site are expected to be included
This is a Phase I two centre study in subjects with PAH WHO functional class III-IV whose symptoms have been clinically stable on their prescribed medical treatment which includes endothelin andor phosphodiesterase type 5 inhibitors for 8 weeks prior to enrollment Such patients will be given either DCA 30 mgkg BID group I 625 mgkg BID group II or 125 mgkg BID group III as an additional treatment for 16 weeks The design is open-label with the subjects acting as their own controls
Primary endpoint is the safety and tolerability of DCA Secondary end points include a functional capacity including a change in the 6 minute walk form baseline b change in pulmonary vascular resistance measured by right heart catheterization c right ventricular volumes and mass measured by MRI d NT-proBNP levels changed from baseline e change in FDG-glucose uptake in the lung and right ventricle measured by PET and f change in quality of life indices
15 evaluable patients in each site are expected to be included
Detailed Description:
The vascular remodeling in PAH is a state of apoptosis-resistance As in cancer a switch from the anti-apoptotic glycolytic metabolism towards the pro-apoptotic oxidative phosphorylation metabolism has been shown to cause regression of vascular remodeling and PAH in several animal models This has been achieved with the small molecular DCA an inhibitor of the mitochondrial enzyme pyruvate dehydrogenase kinase
DCA has been used in humans for over 30 years mostly in the treatment of inherited mitochondrial disorders and is also currently being evaluated as a potential therapy in cancer
This is a first-in-humans Phase I two centre study University of Alberta and Imperial College in subjects with advanced PAH whose symptoms have been clinically stable on their prescribed medical treatment for 8 weeks prior to enrollment These treatments include standard eg diuretics warfarin or specific PAH therapies eg endothelin or phosphodiesterase type 5 inhibitors From the known metabolism of the drugs involved no pharmacokinetic interaction is anticipated In line with most safety and efficacy studies the design is open-label with the subjects acting as their own controls
Patients with PAH who have been stable on their current therapy for the preceding 2 months will be given either DCA 30 mgkg BID group I 625 mgkg BID group II or 125 mgkg BID group III as an additional treatment for 16 weeks Following the baseline visit the patients will be followed every week for the first month and then at weeks 6 8 10 12 and 16 In weeks 1 3 6 and 10 the patients status will be assessed by telephone interview
At all the other visits medical history and physical examination will be performed With the exception of week 2 unless clinically indicated this will be combined with routine hematology and biochemistry and an assessment of functional capacity 6 minute walk test Serum lactate and NT-pro-BNP levels will be measured and PDH activity assay will be performed Urine will be obtained for DCA metabolite studies
At baseline and 16 weeks A cardiac catheterization to assess change in pulmonary hemodynamics a routine cardiac MR RV massvolumes MR angiography FDG-PET to examine for an effect on regional lung or RV glucose uptake
If tolerated well the subjects will continue with their medication and return for follow-up assessments at Weeks 20 24 and 28 At each follow-up visit a physical examination will be performed and functional capacity will be assessed 6 minute walk test At the Week 28 visit a routine cardiac MR will also be performed Enrollment will continue until 30 evaluable subjects 15 in each site are included
DCA has been used in humans for over 30 years mostly in the treatment of inherited mitochondrial disorders and is also currently being evaluated as a potential therapy in cancer
This is a first-in-humans Phase I two centre study University of Alberta and Imperial College in subjects with advanced PAH whose symptoms have been clinically stable on their prescribed medical treatment for 8 weeks prior to enrollment These treatments include standard eg diuretics warfarin or specific PAH therapies eg endothelin or phosphodiesterase type 5 inhibitors From the known metabolism of the drugs involved no pharmacokinetic interaction is anticipated In line with most safety and efficacy studies the design is open-label with the subjects acting as their own controls
Patients with PAH who have been stable on their current therapy for the preceding 2 months will be given either DCA 30 mgkg BID group I 625 mgkg BID group II or 125 mgkg BID group III as an additional treatment for 16 weeks Following the baseline visit the patients will be followed every week for the first month and then at weeks 6 8 10 12 and 16 In weeks 1 3 6 and 10 the patients status will be assessed by telephone interview
At all the other visits medical history and physical examination will be performed With the exception of week 2 unless clinically indicated this will be combined with routine hematology and biochemistry and an assessment of functional capacity 6 minute walk test Serum lactate and NT-pro-BNP levels will be measured and PDH activity assay will be performed Urine will be obtained for DCA metabolite studies
At baseline and 16 weeks A cardiac catheterization to assess change in pulmonary hemodynamics a routine cardiac MR RV massvolumes MR angiography FDG-PET to examine for an effect on regional lung or RV glucose uptake
If tolerated well the subjects will continue with their medication and return for follow-up assessments at Weeks 20 24 and 28 At each follow-up visit a physical examination will be performed and functional capacity will be assessed 6 minute walk test At the Week 28 visit a routine cardiac MR will also be performed Enrollment will continue until 30 evaluable subjects 15 in each site are included
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None