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
|
|
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
|
|
Health Condition / Problems Studied
|
Health Type |
Condition |
Healthy Human Volunteers |
No disease
Taken as control |
Patients |
Newly diagnosed patients of dyslipidimia , |
|
Intervention / Comparator Agent
|
|
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. |