Condition category
Circulatory System
Date applied
14/03/2007
Date assigned
30/03/2007
Last edited
08/08/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

http://www.tishcon.com/

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

Results - basic reporting

Publication summary

2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17824295

Publication citations

  1. 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.

Additional files

Editorial Notes