Track topics on Twitter Track topics that are important to you
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 and/or phosphodiesterase type 5 inhibitors) for 8 weeks prior to enrollment. Such patients will be given either DCA 3.0 mg/kg BID (group I), 6.25 mg/kg BID (group II) or 12.5 mg/kg 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.
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 3.0 mg/kg BID (group I), 6.25 mg/kg BID (group II) or 12.5 mg/kg 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 mass/volumes, 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.
Allocation: Non-Randomized, Control: Dose Comparison, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Pulmonary Arterial Hypertension (Idiopathic, Familial or Anorexigen-associated)
Dichloroacetate Sodium, Dichloroacetate Sodium, Dichloroacetate Sodium
University of Alberta Hospital
Enrolling by invitation
University of Alberta
Published on BioPortfolio: 2014-08-27T03:15:22-0400
OBJECTIVES: I. Determine the pharmacokinetics of sodium dichloroacetate (DCA) in patients with congenital lactic acidemia. II. Determine the efficacy of DCA in decreasing the frequency a...
Patients with the MELAS syndrome experience devastating mental impairment. This study will evaluate the effectiveness of the drug dichloroacetate (DCA) to reduce the symptoms of MELAS.
This is a study to determine the safety of dichloroacetate (DCA) with a low-tyrosine diet given with or without nitisinone (NTBC) in children with chronic lactic acidosis (CLA).
Dichloroacetate (DCA) is a product of water chlorination and a metabolite of certain industrial solvents, thus making it a chemical of environmental concern. However, DCA is also used as a...
The purpose of this study is to identify and analyze the frequency of GSTZ1 haplotypes in a healthy adult population and determine the pharmacokinetics of Dichloroacetate (DCA) metabolism ...
Dichloroacetate (DCA) represents the first targeted therapy for pyruvate dehydrogenase complex deficiency; it is metabolized by glutathione transferase zeta1 (GSTZ1). Variation in the GSTZ1 haplotype ...
To implement and evaluate a clinical practice algorithm to identify preterm infants with sodium deficiency and guide sodium supplementation based on urine sodium concentrations.
OBJECTIVE To compare dialysate sodium concentration and patient plasma sodium concentration of dogs during intermittent hemodialysis treatments. SAMPLE 211 intermittent hemodialysis treatments perform...
To maintain sodium homeostasis, animals will readily seek and ingest salt when salt-depleted, even at concentrations that they typically find aversive when sodium replete. This innate behaviour is kno...
Mechanical stretch increases sodium and calcium entry into myocytes and activates the late sodium current. GS967, a triazolopyridine derivative, is a sodium channel blocker with preferential effects o...
Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.
A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.
Stable sodium atoms that have the same atomic number as the element sodium, but differ in atomic weight. Na-23 is a stable sodium isotope.
A family of membrane proteins that selectively conduct SODIUM ions due to changes in the TRANSMEMBRANE POTENTIAL DIFFERENCE. They typically have a multimeric structure with a core alpha subunit that defines the sodium channel subtype and several beta subunits that modulate sodium channel activity.
Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes.
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza, Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...
Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of affected individuals. Symptoms can range from mild breathles...
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...