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 Table of Contents  
RESEARCH PROTOCOL
Year : 2015  |  Volume : 9  |  Issue : 4  |  Page : 223-229

Protocol for an open-label randomized controlled exploratory trial of Homoeopathy on Dyslipidemia


Director General, Central Council for Research in Homoeopathy, New Delhi, India

Date of Submission26-Nov-2015
Date of Acceptance30-Nov-2015
Date of Web Publication30-Dec-2015

Correspondence Address:
Central Council for Research in Homoeopathy
Director General, Central Council for Research in Homoeopathy, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-7168.172871

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  Abstract 

Background and Objectives: Dyslipidemia refers to the derangements of one or many of the lipoproteins; elevations of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and/or triglycerides (TGL), or low levels of high-density lipoprotein (HDL) cholesterol while elevation of lipoproteins alone is labeled as “hyperlipidemia.” It is a lifestyle disorder of concern today. Statins, fibrates, or a combination of statins with fibrates or niacin have been suggested for their beneficial role in lowering LDL-cholesterol levels, TGL, and increasing HDL-cholesterol levels, but with their adverse effects. Based on the positive results of few studies in the past, this protocol is designed to evaluate the effect of individualized homoeopathic medicines along with therapeutic lifestyle changes (TLC) on serum LDL-cholesterol levels.
Materials and Methods: The study will be a multicentric, open-label, randomized, placebo-controlled exploratory trial. Patients shall be randomized to Homoeopathy or placebo group of intervention using computerized randomization chart. The period of treatment cum follow-up shall be for 6 months. TLC shall be given to both the groups. Primary outcome measure will be to evaluate the changes in LDL-cholesterol levels at 3rd and 6th month from baseline.
Discussion: The study shall help in generating evidence about the role of homoeopathic intervention in dyslipidemia and also help in bringing about behavioral change in people about the adoption of a healthy lifestyle.

Keywords: Dyslipidemia, Exploratory trial, Individualized Homoeopathy, Therapeutic lifestyle changes


How to cite this article:
Central Council for Research in Homoeopathy. Protocol for an open-label randomized controlled exploratory trial of Homoeopathy on Dyslipidemia. Indian J Res Homoeopathy 2015;9:223-9

How to cite this URL:
Central Council for Research in Homoeopathy. Protocol for an open-label randomized controlled exploratory trial of Homoeopathy on Dyslipidemia. Indian J Res Homoeopathy [serial online] 2015 [cited 2019 Jul 24];9:223-9. Available from: http://www.ijrh.org/text.asp?2015/9/4/223/172871


  Introduction Top


Dyslipidemia refers to the derangements of one or many of the lipoproteins; elevations of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and/or triglycerides (TGL), or low levels of high-density lipoprotein (HDL) cholesterol while the elevation of lipoproteins alone is labeled as “hyperlipidemia.” The term “atherogenic dyslipidemia” denotes a combination of elevated TGL and small-dense LDL particles and low levels of HDL-cholesterol. Dyslipidemia may result from over-production or lack of clearance of the lipoprotein particles or may be related to other defects in the apolipoprotein or metabolic enzyme deficiencies. The pathways and means of lipid metabolism in the human body reflect interactions of genetics, complex biochemical processes influenced by medical disorders, medications, and/or environmental factors.[1]

The role of high serum cholesterol, especially a high level of LDL-cholesterol, as a risk factor for coronary artery diseases is well-established.[2] Asian Indians have double the risk of coronary artery diseases than the whites; due to dyslipidemia that is characterized by borderline high TGL, elevated apolipoprotein-B, and reduced HDL in them. It is opined that although the TC levels in Asian Indians is similar or lower as compared to Caucasians, dyslipidemia is more common, which contributes to coronary heart disease (CHD).

The National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) reinforces LDL as the primary target of cholesterol-lowering therapy with the optimal goal of its level below 100 mg/dL. The panel recommends treatment beyond LDL lowering for patients with triglyceride levels of 200 mg/dL and above. Non-HDL-cholesterol, representing the sum of all atherogenic lipoproteins, has been identified as a secondary target of therapy in patients with elevated triglyceride levels. Managing and monitoring non-HDL–cholesterol level is found particularly important for Asian Indians. Lifestyle changes such as maintenance in regular aerobic physical activity, increase intake of Omega -3 polyunsaturated fatty acids in diet, and therapeutic interventions such as statins (HMG-CoA reductase inhibitors), fibrates, or a combination of statins with fibrates or niacin have been suggested for their beneficial role in lowering LDL-cholesterol levels, TGL, and increasing HDL-cholesterol levels, but with their adverse effects.[3]

An observational study conducted by Govekar et al.[4] on hyperlipoproteinemia during April 1992 - March 2003 on 322 patients showed improvement in 290 patients with a reduction in TC and TGL levels in 100 and 37 patients, respectively. Though the study had been carried out on a large number of patients and throws light on the role of indicated homoeopathic medicines on patients with lipoproteinemia, it lacks statistical rigor and power. Another cohort study [5] with 57 patients of hypercholesterolemia treated with complex Homoeopathy showed a significant reduction in lipid parameters. A preclinical study on chickens [6] showed reduction in lipid parameters with homoeopathic medicine Baryta carbonicum and Baryta muriaticum. Another study [7] highlighted the remedial effect of homoeopathic drug S. jambolanum on carbohydrate and lipid metabolic disorders in streptozotocin induced diabetic rats. The lipid lowering effect of Cholesterinum has also been found.[8],[9]

Keeping in view the current scenario of increasing risk of dyslipidemia leading to CHD in Indian population and dearth of conclusive evidence suggesting a beneficial role of Homoeopathy, there is a need to undertake a study for exploring the effectiveness of homoeopathic medicines in dyslipidemia along with TLC.


  Study Objectives Top


Primary Objective

To evaluate the effects of individualized homoeopathic medicines along with TLC on serum LDL cholesterol levels.

Secondary Objective

To evaluate the effects of individualized Homoeopathy + TLC on other serum lipid parameters:

  • TC
  • TGL
  • HDL



  Materials and Methods Top


Settings

The study shall be conducted at seven centers of Central Council for Research in Homoeopathy: Regional Research Institute (H), Gudivada; Central Research Institute (H), Noida, Central Research Institute (H), Kottayam; Drug Standardisation Unit (H), Hyderabad; Clinical Research Unit (H), Tirupati; Clinical Research Unit (H), Puducherry; and Clinical Research Unit (H), Chennai.

Homoeopathic treatment will be given by trained homoeopathic physicians. Dietician/endocrinologist consultants will advise patients about diet and therapeutic lifestyle changes.

The study protocol is in accordance with the latest revision of the Helsinki declaration [10] on human experimentation and good clinical practices of India.[11] Although medicines proposed to be used during the study are known homoeopathic pharmacopoeia preparations, yet necessary clearance of the Ethical Committee and Scientific Advisory Committee has been obtained before undertaking the study. The trial is registered with the clinical trial registry of India (CTRI/2014/12/005257).

Study Design

The study will be a multicentric, open-label, randomized, placebo-controlled exploratory trial. This design shall help in generating a treatment strategy indicated which will further give impetus for carrying out a double blind trial.

This study shall have two groups:

Group 1: Individualized homoeopathic treatment + TLC.

Group 2: Placebo Control + TLC.

Selection of Patients

Patients shall be screened as per the criteria given in [Table 1].
Table 1: Eligibility criteria

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Randomization and Allocation

The patients shall be assigned to one of the intervention groups with the aid of computer generated random numbers, using block randomization, generated at headquarters by the coordinator along with the biostatistician.

Intervention

Each patient will be assessed after a detailed case taking as per the case recording format (CRF) and shall be given homoeopathic treatment as per the guidelines laid down by Hahnemann in the 5th edition of Organon of Medicine if he is allocated to Group I. In group II i.e., placebo, unimpregnated globules shall be dispensed to patients.

Selection of medicine will be made depending on the totality of symptoms. Use of appropriate repertory shall be done wherever required. Selection of potency and repetition of medicine will be as per discretion of investigator and as per patient's condition.

Concomitant Therapy

TLC includes physical activity and diet modification which shall be given to all the patients after eliciting baseline diet, physical activity information in consultation with the dietician/endocrinologist.

Treatment Regimen/Repetition Schedule

Individual homoeopathic medicines will be administered orally. The medicine will be repeated depending on the potency and complaints of the patient in accordance with the principles of Homoeopathy. Once the improvement sets in placebo will be continued until the medicine continues to act.

Follow-up

The enrollment period will be for 6 months, and each enrolled patient shall be followed every month for a period of 6 months. Required investigations of each patient shall be conducted at baseline 3rd and 6th month [Table 2]. Physical activity of patient will be assessed by physical activity scoring system [12] every month as a part of TLC. Dietician/endocrinologist will advise patients about diet and therapeutic lifestyle changes during the study and adherence will be assessed by diet adherence score [12] at every month.
Table 2: Time line and schedule of enrollment, intervention, and assessment

Click here to view


Early Withdrawal of Patients

Patients developing any cardiac event, frank diabetes, any systemic illness (cancer, hepatic diseases, renal diseases, diabetes, HIV, any abnormality in liver function test, and kidney function test, unwilling to participate further, or with any other issue as per the discretion of investigator shall be withdrawn from the study.

Patient Compliance Monitoring

All the patients shall be motivated to adhere to study treatment and for measurement of various investigations from time to time by the investigator. To check the compliance a telephonic recall about adherence to diet and exercise shall be given to the patient every week.

Study Monitoring

The study will be monitored on regular basis. Monthly assessments of case records at headquarters as well as on-site visits from time to time will be carried out.


  Study Outcomes Top


Primary Study Endpoint (Primary Outcome Measure)

  • To evaluate the changes in LDL-cholesterol levels at 3rd and 6th month from baseline.


Secondary Study Endpoints (Secondary Outcome Measures)

To evaluate the changes in:

  • TC at 3rd and 6th month from baseline
  • TGL at 3rd and 6th month from baseline
  • HDL at 3rd and 6th month from baseline.



  Data Collection Top


Standard CRF and predesigned spread sheet shall be used for data capturing. Data recording shall be done through validated scoring systems and results of timely investigations.

Sample Size Determination

Being an exploratory study, there is no definite calculation of sample size; however, in this study, 100 patients (50 in each group) shall be enrolled. With dropout rate of 20%, the total sample size shall be 120 (60 in each group).

Statistical Methods/Statistical Evaluation

The principal analyses of primary and secondary outcomes will employ the “intent-to-treat” approach. All the data shall be assessed for normal distribution. All statistical tests will be done as follows: Non-parametric tests for categorical data, ordinal data, and parametric test for continuous data.


  Discussion Top


Lifestyle disorders are diseases of civilization. As can be understood, they are caused by an inappropriate relationship of people with their environment and their own genetic/familial/inherited tendencies to suffer from a diseased condition. Hyperlipidemia/dyslipidemia, mostly an asymptomatic disease, is a progressing lifestyle disorder today and needs to be managed with timely medical treatment and lifestyle modification before it leads to its complications.

Very few clinical,[4],[5] preclinical studies [6],[7],[8] and case reports [9],[13],[14] in the past with their own strengths and weaknesses reflect the positive directions of using homoeopathic medicines in hyperlipidemia, however no systemic reviews and controlled clinical trials have been carried out till date to explore and reckon its effectiveness/efficacy.

This study protocol is designed as a randomized controlled trial with comparator arm as placebo along with TLC in both the groups and shall help in generating evidence about the role of homoeopathic intervention in hyperlipidemia. Medicines prescribed as per homoeopathic principles covering the entire symptomatology and individual aspects of each patient shall be helpful in improving the overall health and well-being of the patient. Further, the response of the effects of the remedies prescribed shall be helpful in developing an effective treatment strategy. It is also expected that the information on behavioral change for healthy life style (regular physical activity in the form of walk/yoga, consumption of healthy diet and avoidance of tobacco and alcohol etc.) given to the patients shall also inculcate a sense of self-care which is the need of the hour.

The protocol shall generate data that can be reported as per CONSORT guidelines for reporting randomized trials with parallel groups,[15] and the reporting data on a homoeopathic treatments (RedHot) supplement to CONSORT.[16] It is in accordance with the SPIRIT 2013.[17] Further, this study involves administration of individualized homoeopathic medicine with the involvement of homoeopathic experienced doctors in treating patients suffering from dyslipidemia, using validated assessments which will be amenable to the profession at large thus covering all the domains of model validity of homoeopathic trials.[18]


  Trial Status Top


The study is in the pretrial phase in which 1469 patients have been screened, and 156 patients have been enrolled till date.


  Contributors Top


Study concept and design: V.A. Siddiqui 1, Praveen Oberai 2, Varanasi Roja 3, Rupali Bhalerao 4

Drafting of manuscript: Anupriya 5, Varanasi Roja 3

Critical review of manuscript: Raj K. Manchanda 6, Praveen Oberai 2

Statistical planning: Maya Padmanabhan 7

Funding/Support: Central Council for Research in Homoeopathy

1 Former Assistant Director (H)/Scientist-4, Central Research Institute (Homoeopathy), Noida

2 Research Officer (H)/Scientist-4, Central Council for Research in Homoeopathy

3 Research Officer (H)/Scientist-2, Central Council for Research in Homoeopathy

4 Research Associate (H), Central Council for Research in Homoeopathy

5 Research Associate (H), Central Council for Research in Homoeopathy

6 Director General, Central Council for Research in Homoeopathy

7 Statistical Assistant, Central Council for Research in Homoeopathy

Financial Support and Sponsorship

Central Council for Research in Homoeopathy

Conflicts of Interest

There are no conflicts of interest.

 
  References Top

1.
Misra A, Luthra K, Vikram NK. Dyslipidemia in Asian Indians: Determinants and significance. J Assoc Physicians India 2004; 52:137-42.  Back to cited text no. 1
    
2.
Enas EA, Mohan V, Deepa M, Farooq S, Pazhoor S, Chennikkara H. The metabolic syndrome and dyslipidemia among Asian Indians: A population with high rates of diabetes and premature coronary artery disease. J Cardiometab Syndr 2007; 2:267-75.  Back to cited text no. 2
    
3.
Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Executive summary of the third report of the national cholesterol education program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001; 285:2486-97.  Back to cited text no. 3
    
4.
Govekar JP, Paul VK, Singh K, Oberai P, Roja V. Hyperlipoproteinemia. Clinical Research Studies – Series II: New Delhi: CCRH; 2009. p. 63-70.  Back to cited text no. 4
    
5.
Pay PN. Homoeopathy in hypercholesterolaemia. Br Homeopath J 1980; 69:161-2.  Back to cited text no. 5
    
6.
M. Nandi, D. Raha. Dose-dependent effect of Baryta carbonicum and Baryta muriaticum in homœopathic trituration on experimentally induced high serum lipid concentration in chickens. British Homoeopathic journal 1990; 79(4):224–7.  Back to cited text no. 6
    
7.
Maiti S, Ali KM, Jana K, Chatterjee K, De D, Ghosh D. Ameliorating effect of mother tincture of Syzygium jambolanum on carbohydrate and lipid metabolic disorders in streptozotocin-induced diabetic rat: Homoeopathic remedy. J Nat Sci Biol Med. 2013 Jan; 4(1):68-73.  Back to cited text no. 7
    
8.
Dixit V P. Role of cholesterinum and clofibrate in correcting increased lipid levels. Indian journal of pharmaceutical Sciences 1986; 48(3):60-3.  Back to cited text no. 8
    
9.
Kamath M.K. Evidence of effective treatment in Homoeopathy for Hyperlipidemia, Asian Journal of Homoeopathy 2008, 48-50.  Back to cited text no. 9
    
10.
World Medical Association. World medical association declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2013;310:2191-4.  Back to cited text no. 10
    
11.
Ethical Guidelines for Biomedical Research on Human. Indian Council of Medical Research, New Delhi; 2006. Available from: http://www.icmr.nic.in/ethical_guidelines.pdf. [Last cited on 2015 Oct 07].  Back to cited text no. 11
    
12.
Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V; Indian diabetes prevention programme (IDPP). The Indian diabetes prevention programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia 2006; 49:289-97.  Back to cited text no. 12
    
13.
Karo W. Arteriosclerosis. The Hahnemannian Gleanings 1983; 534-37.  Back to cited text no. 13
    
14.
Ghosh A. Ageing, arteriosclerosis, dizziness and Baryta carb. British Homoeopathic journal 1979; 68(4):178-80.  Back to cited text no. 14
    
15.
Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:332.  Back to cited text no. 15
    
16.
Dean ME, Coulter MK, Fisher P, Jobst KA, Walach H. Reporting data on homoeopathic treatments (RedHot): A supplement to CONSORT. J Altern Complement Med 2007; 13:19-23.  Back to cited text no. 16
    
17.
Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: Guidance for protocols of clinical trials. BMJ 2013; 346:7586.  Back to cited text no. 17
    
18.
Mathie RT, Roniger H, Van Wassenhoven M, Frye J, Jacobs J, Oberbaum M, et al. Method for appraising model validity of randomised controlled trials of homoeopathic treatment: Multi-rater concordance study. BMC Med Res Methodol 2012; 12:49.  Back to cited text no. 18
    



 
 
    Tables

  [Table 1], [Table 2]


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