Contact information
Type
Scientific
Primary contact
Dr Adarsh Kumar
ORCID ID
Contact details
Professor and Head of the Department of Cardiology
Government Medical College Amritsar
Punjab
143001
India
adarshk27@jla.vsnl.net.in
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
The TISHCON Study
Study hypothesis
Chronic Heart Failure (CHF) represents a major public health burden, and its prognosis is comparable to that of different malignant diseases. CHF progresses because of the activation of neurohormones and pro-inflammatory cytokines, as well as coenzyme Q10 (CoQ) deficiency, following an initial cardiac injury such as Acute Myocardial Infarction (AMI), statin toxicity or a mutation of the genetic programme. It is becoming increasingly apparent that inflammatory mediators play a crucial role in the development of CHF and AMI and several strategies to counterbalance different aspects of the inflammatory response are considered. Possible targets involve pro-and anti-inflammatory cytokines and their receptors, endotoxin, adhesion molecules, nitric oxide and nitric oxide synthase, reactive oxygen species, CoQ and L-carnitine in mitochondria and different types of leucocytes.
The most important cytokines implicated in the progression of CHF are Tumour Necrosis Factor (TNF-alpha), Interleukin (IL)-1, and IL-6. These cytokines share some of their major characteristics (redundancy), and all act in a pro-inflammatory sense. Among those, TNF-alpha is the cytokine that has been studied in greatest detail. IL-10 is anti-inflammatory which is beneficial in heart failure. Cytokines form a vast array of relative low molecular weight, pharmacologically active proteins. These substances are secreted by different cell types for the purpose of altering either their own function (autocrine) or that of adjacent cells (paracrine). Several hypotheses have been suggested to describe the origin of immune activation in CHF. The production of pro-inflammatory cytokines has mostly been attributed to secretion by mononuclear cells, although the myocardium seems to be another important source. Some evidence suggests that catecholamines augment this myocardial cytokine production. There is evidence that CoQ and carnitine may be beneficial in patients with heart failure.
In the present study, we examine, that ubiquinol, in conjunction with L-carnitine, can decrease cytokines and may be useful in patients with CHF.
Ethics approval
Reviewed and approved by the Institutional Ethics Committee at Government Medical College, Amritsar, India on the 28th August 2005.
Study design
Double blind, placebo controlled, randomised trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Chronic Heart Failure
Intervention
Nine carni Q-gel softgels (three with each meal thrice daily), which provide a total of 270 mg ubiquinol and 2250 mg L-carnitine daily, or nine matching placebos were administerd to each patient, during the period of 12 weeks. All patients were kept on standard drug therapy, and carni Q-gel and placebo were used as adjuncts to regular drug therapy not as a replacement or substitute.
Laboratory data:
Baseline measurements were taken and repeated after 12 weeks, and a complete blood profile was performed including:
1. Thiobarbituric Acid Reactive Substances (TBARS) and Malondialdehyde (MDA) were obtained by colorimetric methods
2. Resting electrocardiogram and prothrombin time (on anticoagulants) were performed in all the patients at baseline and during follow up whenever indicated
3. CoQ levels in the serum were measured by high pressure liquid chromatography based on an earlier method at Tishcon Corporation (USA)
4. Cytokines Interleukin-six (IL-6), Interleukin-ten (IL-10) and Tumour Necrotising Factors (TNF)-alpha were determined by using a solid phase, two sided chemiluminescence enzyme immunometric assay (immulite automated analyser) kit
The serum samples were kept at -24°C until assay. Results were expressed in pg/ml. The technicians measuring the laboratory data were blind to the groups.
Intervention type
Drug
Phase
Not Specified
Drug names
Ubiquinol and carnitine
Primary outcome measure
1. Increase in distance walked in six minutes
2. NYHA class of heart failure
3. Echocardiographic cardiac size
Secondary outcome measures
Reduction in TNF-alpha and IL-6
Overall trial start date
01/09/2005
Overall trial end date
30/09/2006
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Both men and women affected by Chronic Heart Failure (CHF) of mixed etiology
2. Ischaemic, hypertensive, valvular heart disease and idiopathic dilated cardiomyopathy
3. Severity of disease was assessed by New York Heart Association (NYHA) functional Class II to IV
Participant type
Patient
Age group
Not Specified
Gender
Both
Target number of participants
62
Participant exclusion criteria
1. Hypertrophic cardiomyopathy
2. Amyloid cardiomyopathy
3. Not willing to give consent
4. Patients presenting with shock
5. Chronic renal failure
6. Cancer
Recruitment start date
01/09/2005
Recruitment end date
30/09/2006
Locations
Countries of recruitment
India
Trial participating centre
Professor and Head of the Department of Cardiology
Punjab
143001
India
Sponsor information
Organisation
Tishcon Corporation (USA)
Sponsor details
c/o Mr Raj K Chopra
Westbury
New York
11590
United States of America
+1 516 333 3050
Raj@Tishcon.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Tishcon Corporation (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17824295
Publication citations
-
Results
Kumar A, Singh RB, Saxena M, Niaz MA, Josh SR, Chattopadhyay P, Mechirova V, Pella D, Fedacko J, Effect of carni Q-gel (ubiquinol and carnitine) on cytokines in patients with heart failure in the Tishcon study., Acta Cardiol, 2007, 62, 4, 349-354.