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CTRI Number  CTRI/2017/11/010341 [Registered on: 02/11/2017] Trial Registered Retrospectively
Last Modified On: 31/10/2017
Post Graduate Thesis  Yes 
Type of Trial  Observational 
Type of Study   Follow Up Study 
Study Design  Other 
Public Title of Study   Role of Adipsin in the Mechanism of Glucose Intolerance by Statin Therapy 
Scientific Title of Study   A Prospective Study to Explore the Role of Adipsin in the Mechanism of Glucose Intolerance Developed as an Adverse Effect of Statin Therapy 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Jahnavi Maini 
Designation  Post Graduate 
Affiliation  Lady Hardinge Medical College 
Address  Department Of Pharmacology Lady hardinge Medical College Shaheed Bhagat Singh Road Connaught Place Delhi

Central
DELHI
110001
India 
Phone  9582976766  
Fax    
Email  jahnavi.maini@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Harmeet Singh Rehan 
Designation  Director Professor 
Affiliation  Lady Hardinge Medical College 
Address  Department Of Pharmacology Lady Hardinge Medical College Shaheed Bhagat Singh Road Connaught Place Delhi

Central
DELHI
110001
India 
Phone  9811694040  
Fax    
Email  harmeetrehan@hotmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Jahnavi Maini 
Designation  Post Graduate 
Affiliation  Lady Hardinge Medical College 
Address  Department Of Pharmacology Lady hardinge Medical College Shaheed Bhagat Singh Road Connaught Place Delhi


DELHI
110001
India 
Phone  9582976766  
Fax    
Email  jahnavi.maini@gmail.com  
 
Source of Monetary or Material Support  
Department Of Pharmacology Lady Hardinge Medical College Shaheed Bhagat Singh Road Connaught Place New Delhi-110001 
 
Primary Sponsor  
Name  Dr Jahnavi Maini 
Address  Department Of Pharmacology Lady Hardinge Medical College Shaheed Bhagat Singh Road Connaught Place New Delhi-110001 
Type of Sponsor  Government medical college 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 2  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Jahnavi Maini  Department of Medicine  Lady Hardinge Medical College & associated Smt. Sucheta Kriplani Hospital Shaheed Bhagat Singh Road Connaught Place Delhi 110001
Central
DELHI 
9582976766

jahnavi.maini@gmail.com 
Dr Jahnavi Maini  Department of Pharmacology  Lady Hardinge Medical College Shaheed Bhagat Singh Road Connaught Place, Delhi 110001
Central
DELHI 
9582976766

jahnavi.maini@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethical Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Healthy Human Volunteers  No disease Taken as control 
Patients  Newly diagnosed patients of dyslipidimia ,  
 
Intervention / Comparator Agent  
Type  Name  Details 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  Treatment naive dyslipidemic patients (Low-density lipoprotein ≥100mg/dl) or patients with ASCVD having dyslipidemia requiring statin therapy.
 
 
ExclusionCriteria 
Details  1. Patient with comorbid Type 1 and Type 2 Diabetes Mellitus.
2. Patients prescribed lipid lowering agents other than statins.
3. Any known history of condition(s) which may cause secondary dyslipidemia (e.g. nephrotic syndrome, glycogen storage disease etc.).
4. Any history of condition(s) which may affect euglycemia (pancreatic impairment or disease).
5. History of previous or current muscular or neuromuscular disease.
6. History of drugs which impair lipid profile or glycemic parameters.

 
 
Method of Generating Random Sequence    
Method of Concealment    
Blinding/Masking    
Primary Outcome  
Outcome  TimePoints 
1. To estimate and compare the change in serum adipsin levels in dyslipidemic patients from baseline with that of serum adipsin levels after 12 weeks of statin therapy  12 weeks 
 
Secondary Outcome  
Outcome  TimePoints 
To estimation and comparison of serum levels of adipsin (mean ± SD) in statin treatment group and NHV  baseline 
2. To study the correlation of serum adipsin levels with serum insulin & HbA1c levels following 12 weeks of statin therapy  12 weeks 
 
Target Sample Size   Total Sample Size="55"
Sample Size from India="55" 
Final Enrollment numbers achieved (Total)= "55"
Final Enrollment numbers achieved (India)="55" 
Phase of Trial   N/A 
Date of First Enrollment (India)   03/12/2015 
Date of Study Completion (India) 30/03/2017 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="5"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   not applied 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

Statins, well established group of lipid lowering drugs, are widely employed in contemporary approaches for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD).[1-4]

Statins are usually well tolerated by the patients but are associated with wide range of adverse drug reactions like myalgia, rhabdomyolysis, impaired cognition, hepatotoxicity and neuropathy.[5-8] Recent studies and meta-analysis have reported that the use of statins modestly increased the risk of diabetes as compared to placebo.[9] However, little is known about the mechanism involved in their diabetogenic effect. Yada et al found that statins inhibit the glucose-induced calcium signaling-dependent insulin secretion leading to diabetogenic effect.[10] In addition, statins suppress the synthesis of ubiquinone (CoQ10), an essential factor in the mitochondrial electron-transfer system, resulting in reduced production of adenosine tri-phosphate (ATP) which inhibits insulin secretion.[11] Furthermore, Nakata et al demonstrated that statins decrease the expression of glucose transporter type 4 (Glut4) on adipocytes, resulting in impaired glucose tolerance.[12]

Adipsin is an adipokine, earlier known as complement factor D which has recently been postulated to have a role in maintaining β cell function. Adipsin generates peptide C3a which acts on islets to augment ATP levels, respiration and cytosolic free Ca2+ leading to insulin secretion.[13] In a recent clinical study, Bhandari et al studied 218 proteins in serum of 11 patients receiving statins for primary prevention of cardiovascular risk and reported downregulation of adipsin protein.[14] It is established that adipsin modulate pancreatic β-cell function.[13]  This warrants the need to study the effect of statin therapy on serum adipsin levels which may give an insight to understand the mechanism of development of glucose intolerance following statin use.

LACUNAE IN KNOWLEDGE

Various mechanisms have been proposed to explain how statins increase the risk of new onset diabetes. However, how statins modulate serum adipsin levels and beta cell function is not available in literature.

Study protocol was approved by the Institutional Ethical Committee of Lady Hardinge Medical College, New Delhi (Annexure I). Treatment naive patients of dyslipidemia started on statins and fulfilling aforementioned inclusion and exclusion criteria were enrolled. NHV were also screened for inclusion and exclusion criteria before enrollment. Written informed consent was obtained from all the enrolled patients as well as NHV. The selection of statin and its dose was purely a decision of the treating physician.

Patients’ profile, demography, medical history and treatment history was recorded in Clinical Record Form (Annexure II). Venous blood sample of each patient in the statin treatment group and in the NHV group was taken to assess baseline serum adipsin and insulin levels by enzyme-linked immunosorbent assay (ELISA). Other baseline investigations like Liver Function Test (LFT), Kidney Function Test (KFT), Complete Blood Count (CBC), Lipid profile, HbA1c, Fasting blood sugar (FBS) and Post prandial blood sugar (PPBS) levels were additionally recorded in the individual Investigation Performa (Annexure III). These parameters were repeated only in the statin treatment group after 12 weeks of statin therapy. The patients were asked to visit the Medical-OPD for follow up after 4 weeks, 8 weeks and 12 weeks of initiation of statin therapy (Table 1) for routine clinical examination (Annexure IV) and for monitoring the appearance of any adverse drug reaction (ADR) (Annexure V). Any suspected ADR was recorded in ADR reporting form of Pharmacovigilance Programme of India (PvPI) (Annexure VI).

 

Table 1: Follow up visit schedule and investigation plan for the statin treatment group.

 

Parameters

Follow up visit schedule

Visit 1

 

Visit 2

 

Visit 3

 

Visit 4

Day from start of therapy

0

(Enrollment)

 

4 weeks

8 weeks

12 weeks

Patient’s profile

√

×

×

×

Demography

√

×

×

×

S. Adipsin

√

×

×

√

S. Insulin

√

×

×

√

FBS and PPBS

√

×

×

√

HbA1c

√

×

×

√

Lipid profile

√

×

×

√

LFT/KFT/CBC

√

×

×

√

ADR Monitoring

×

√

√

√

Clinical examination

√

√

√

√


RESEARCH QUESTION

Does statin therapy influence serum adipsin levels?

 HYPOTHESIS

Statin therapy decreases serum adipsin levels leading to glucose intolerance.

AIMS AND OBJECTIVES

1.     To study the effect of statin therapy on serum adipsin levels.

2.     Correlate the levels of adipsin with serum insulin levels and HbA1c.

 
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