The Effects of Peroxisome Proliferators Activated Receptor-Gamma (PPAR-γ) Agonists on Certain Biochemical and Inflammatory Markers in Metabolic Syndrome

This study has been completed.
Sponsor:
Information provided by:
Aligarh Muslim University
ClinicalTrials.gov Identifier:
NCT00926341
First received: June 22, 2009
Last updated: June 23, 2009
Last verified: June 2009
  Purpose

Metabolic syndrome, labeled as the world's latest epidemic, is the force behind the global epidemic of Type 2 Diabetes Mellitus and Cardio Vascular Diseases. This emerging epidemic is an important public health problem for South Asians in their homeland and worldwide.

Pharmacological therapy is a critical step in the management of patients with metabolic syndrome. In general, treatment for metabolic syndrome, that targets all or most of the components of metabolic syndrome is either deficient or non-existent. The study presented here is the pioneering work in the management of metabolic syndrome, the emerging global epidemic.


Condition Intervention Phase
Metabolic Syndrome
Drug: Pioglitazone
Drug: Telmisartan
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study on the Effects of Peroxisome Proliferators Activated Receptor-γ Agonists on Certain Biochemical and Inflammatory Markers in Patients With Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by Aligarh Muslim University:

Primary Outcome Measures:
  • Control of blood pressure and decline in triglycerides level [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Improvement in Inflammatory markers Hs-CRP, TNF-alpha, IL-6 and visceral obesity [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 110
Study Start Date: October 2006
Study Completion Date: September 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Active control
1. Active Control: (n=20), intervention: no intervention
Active Comparator: PIO arm
PIO arm (n=30), Pioglitazone 30 mg/day, given for 24 weeks.
Drug: Pioglitazone
Tab. Pioglitazone-30 mg/day, oral, 24 weeks
Active Comparator: Telmi arm
Telmia arm (n=30): Tab. Telmisartan 40 mg/day given for 2 weeks.
Drug: Telmisartan
Tab. Telmisartan- 40 mg/day, oral, 24 weeks

Detailed Description:

Our understanding of the metabolic syndrome has been improved by the discovery nuclear peroxisome proliferator-activated receptors (PPARs). PPAR-γ is a nuclear receptor that influences the expression of multiples gene involved in carbohydrate and lipid metabolism. At the crossroads of obesity, insulin resistance, and cardiovascular disease is the nuclear receptor PPAR-γ. At present, metabolic syndrome can be described as a 'PPAR-γ agonist resistance syndrome.' The modulation of PPAR-gamma activity is an interesting therapeutic approach to address multi-component metabolic syndrome and its consequent cardiovascular events.

Recent studies have indicated that in addition to anti diabetic properties, PPAR-γ agonists (TZD)-Pioglitazone, provides protection against atherosclerotic cardiovascular disease. Further, the identification of ARBs-Telmisartan and Irbesartan, as capable of activating PPAR − γ, has provided a novel approach in treating hypertension, insulin resistance, hyperlipidemia, and inflammation.

Emerging evidence suggests that PPAR-γ agonist: Thiazolidinediones (TZD)-Pioglitazone is an insulin sensitizer and modulator of metabolic syndrome, through its pleiotropic effects on vascular risk and have beneficial effects on systemic inflammatory markers. Despite the beneficial effects of full PPAR- agonists like the TZDs, recent evidence suggests that full PPAR- agonists are less than optimal agents in patients with metabolic syndrome. TZDs promote adipo-genesis and fluid retention, causing weight gain and precipitate congestive heart failure. The adverse effects of full PPAR- agonists like the TZDs have reinforced the need to identify additional therapies with insulin-sensitizing properties. The recent discovery that telmisartan, an angiotensin II type 1 receptor (AT1-R) blockers (ARBs), is uniquely capable of selective PPAR- -modulating activities, have the potential to treat both hemodynamic and biochemical features of insulin resistance and metabolic Syndrome.

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with at least 3 out of 5 criteria of metabolic syndrome of NCEP-ATP III (Asian-Pacific) guideline:

    1. Waist circumference of > 90 cm in men or > 80 cm in women;
    2. Serum triglycerides of >= 150 mg/dl;
    3. High-density lipoprotein-cholesterol (HDL-C) levels of < 40 mg/dl in men and < 50 mg/dl in women;
    4. Fasting glucose of 6.1/ m.mol (≥l00 mg/dl)
    5. Systolic blood pressure > = 130 mmHg or Diastolic blood pressure >= 85 mmHg or OR on anti-hypertensive therapy
  • Ability to perform all tasks related to glycemic control and risk factor management.
  • Written informed consent.
  • Between 30 and 70 years of age of either sex.

Exclusion Criteria:

  • Concomitant use of ACE inhibitor or ARB in the last 3 months. Or angioedema with ACE I / ARB or uncontrolled hypertension (SBP >=160 mmHg and/or DBP >=100 mmHg) or known case of secondary hypertension.
  • Patients already taking any thiazolidinediones or having contraindications for the same.
  • Class III or IV heart failure
  • Renal dysfunction as defined by serum creatinine > 130umol/L (> 2.0 mg/dl)
  • Concomitant use of statin or fenofibrate.
  • Hepatic dysfunction as defined by SGPT (ALT)> 3 times the upper limit of normal
  • Taking Anti-obesity medications/metformin
  • History of drug or alcohol dependency within six months.
  • History of active malignancy, chronic,inflammatory disorder, or chronic infections which would interfere with protocol completion.
  • Use of systemic glucocorticosteroids/aspirin/anti-inflammatory drugs.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00926341

Locations
India
Department of Medicine, J.N.Medical,College, AMU,Aligarh
Aligarh, Uttar Pradesh, India, 202002
Sponsors and Collaborators
Aligarh Muslim University
Investigators
Principal Investigator: Shahzad F HAQUE, MBBS.MD Department of medicine,JNMC, AMU, ALIGARH
  More Information

Additional Information:
Publications:
Responsible Party: DR.S.F.Haque,Reader,, Department of Medicine, JNMC,AMU
ClinicalTrials.gov Identifier: NCT00926341     History of Changes
Other Study ID Numbers: SFH-CASR-FMD-06
Study First Received: June 22, 2009
Last Updated: June 23, 2009
Health Authority: India:Institutional Review Board , J.N.Medical College,Faculty of Medicine, AMU. ALIGARH ':'

Keywords provided by Aligarh Muslim University:
Metabolic syndrome
inflammatory markers
Thiazolidinediones
Angiotensin receptor blockers

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pioglitazone
Telmisartan
Angiotensin Receptor Antagonists
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014