Lifestyle Intervention Targetting Obesity and Insulin Resistance in Chronic Hepatitis C

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Lifestyle Intervention Targetting Obesity and Insulin Resistance in Chronic Hepatitis C
This study is currently recruiting participants.
Verified by University Health Network, Toronto, November 2008

Sponsored by: University Health Network, Toronto
Information provided by: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00755742

Purpose

Chronic hepatitis C (CHC) infection affects approximately 1 in 100 Canadians. Untreated, CHC has significant long-term consequences including cirrhosis, liver cancer and liver failure. CHC is intrinsically linked to both obesity and insulin resistance (IR) or "pre-diabetes", their co-existence worsens overall health outcomes. We have demonstrated that obesity (BMI ≥30kg/m2) is over twice as common amongst patients with CHC (28.8%) compared with the general Canadian population. Obesity superimposed on CHC reduces the success of antiviral treatment and promotes liver scarring (hepatic fibrosis), fatty liver (steatosis) and increases the risk of liver cancer. Both CHC and obesity contribute to IR putting these patients at risk of type 2 diabetes.

IR, like obesity in CHC, reduces antiviral success rates. We have shown that diabetics are at higher risk of developing liver cancer compared with non-diabetics. It is therefore timely to address lifestyle modification to delay the onset of diabetes. We will examine the impact of a multidisciplinary lifestyle program on the insulin resistance in 50 obese "pre-diabetic" patients with current or past CHC. The 24 week program comprises an individualized nutritional and exercise plan supported by behavior modification counseling. Through gaining a better understanding of links between obesity, insulin resistance and hepatitis C infection we hope to delay the onset of diabetes and reduce the likelihood of all their untoward effects on the liver.

Condition: Hepatitis C, Insulin Resistance, Metabolic Syndrome, Obesity
Intervention: Lifestyle Intervention

Study Type: Interventional
Study Design: Efficacy Study, Open Label, Parallel Assignment, Treatment
Official Title: Evaluation of the Impact of a Combined Program of Diet, Exercise and Behavior Modification on the Insulin Resistance and Adipokine Profile in Obese Patients With Current and Cured Chronic Hepatitis C.

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:

* HOMA-IR [ Time Frame: 12, 24 and 28 weeks ] [ Designated as safety issue: No ]


Secondary Outcome Measures:

* TNF-alpha [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* leptin [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* adiponectin [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* fatigue score [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* mood score [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* cholesterol [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* Metabolic Syndrome [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* HDL-cholesterol [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* LDL-cholesterol [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* RBC fatty acid composition [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* BMI [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* Waist circumference [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]
* triglycerides [ Time Frame: 12, 24, 28 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: November 2008
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)

Group 1 - HCV RNA positive: Experimental
25 obese and insulin resistant, non-cirrhotic, non-diabetic, non-genotype 3 patients with chronic hepatitis C (HCV RNA positive) will undergo 24 week lifestyle intervention comprising diet, physical activity (monitored by pedometers) in combination with behavior modification counseling. This arm includes patients who are naive to antiviral therapy, relapsed or not responded to antiviral therapy.

Assigned Intervention:

Lifestyle intervention

The 3-pronged lifestyle intervention is designed to deliver a period of intensive contact (week 0-12) and less-intensive contact (weeks 12-24) with follow-up at week 28. i) Behavior Modification Counseling The principles of motivational enhancement therapy (MET) and behavior therapy component of cognitive-behavior therapy (CBT) will be utilized at each face-to-face visit and telephone contact to provide individually tailored counseling to enhance internal motivation and facilitate behavior change toward diet and physical activity improvements that are adaptable to each participant's usual habits.

ii) Physical activity assessment and exercise prescription Physical activity target: increment in activity of at least 3000 steps per day above the baseline, or total activity of 10,000 steps per day (whichever is greater). iii) Dietary assessment and nutritional plan: A diet plan designed to both lose weight and improve insulin resistance will be provided.

Group 2 - HCV RNA negative: Active Comparator
25 obese and insulin resistant, non-cirrhotic, non-diabetic, non-genotype 3 patients with cured chronic hepatitis C (HCV RNA negative) will undergo 24 week lifestyle intervention comprising diet, physical activity (monitored by pedometers) in combination with behavior modification counseling. This arm includes patients who have cleared hepatitis C virus with previous antiviral therapy.

Assigned Intervention:

Lifestyle intervention

The 3-pronged lifestyle intervention is designed to deliver a period of intensive contact (week 0-12) and less-intensive contact (weeks 12-24) with follow-up at week 28. i) Behavior Modification Counseling The principles of motivational enhancement therapy (MET) and behavior therapy component of cognitive-behavior therapy (CBT) will be utilized at each face-to-face visit and telephone contact to provide individually tailored counseling to enhance internal motivation and facilitate behavior change toward diet and physical activity improvements that are adaptable to each participant's usual habits.

ii) Physical activity assessment and exercise prescription Physical activity target: increment in activity of at least 3000 steps per day above the baseline, or total activity of 10,000 steps per day (whichever is greater). iii) Dietary assessment and nutritional plan: A diet plan designed to both lose weight and improve insulin resistance will be provided.

Eligibility

Ages Eligible for Study: 18 Years to 65 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

* obese (BMI >/= 30)
* insulin resistant (HOMA-IR >/= 2.1)

Exclusion Criteria:

*

Cirrhotic patients: biopsy proven OR fibrotest >0.8 (calculated using α-2 macroglobulin, apolipoprotein A, haptoglobin, GGT, bilirubin and age).
o Genotype 3 patients
o Women with ongoing pregnancy or who are breast-feeding
o Patients with any other other underlying liver disease (viral, alcoholic, druginduced, autoimmune, metabolic, genetic).
o Patients currently on antiviral therapy, or who have ceased therapy within 6 months of recruitment to the study.
o Patients with other causes for insulin resistance e.g., excess counter-regulatory hormones: glucocorticoids, catecholamines, growth hormone, polycystic ovary syndrome).
o Patients on steroids or other drug that affects insulin resistance, which are unable to be stopped for 3 days prior to IR testing.
o Patients with overt diabetes (based on results of fasting plasma glucose) will be excluded from participation as we are focusing on insulin resistance in the absence of diabetes.
o

Conditions which preclude a sudden increase in physical activity:
+ History or other evidence of chronic pulmonary disease associated with functional limitation.
+ History of severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases).
+ Unable to 10000 steps/day eg physical disability, morbid obesity.
o Evidence of ongoing substance use (including alcohol consumption >20g/day for men and >10g/day for women) within one year of study recruitment.
o Poor veins (inadequate venous access)
o Inability or unwillingness to provide informed consent or abide by study requirements eg severe psychiatric illness, lives remotely, time commitment.

Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00755742

Contacts
Contact: Elizabeth J Heathcote, MD FRCPC 416-603-5914
Contact: Venessa Pattullo, MB BS FRACP 416 603 5800 ext 3234

Locations:
Canada, Ontario
Toronto Western Hospital, University Health Network
Toronto, Ontario, Canada, M5T2S8

Principal Investigator: Elizabeth J Heathcote, MD FRCPC
Sub-Investigator: Venessa Pattullo, MB BS FRACP
Sub-Investigator: Sanjeev Sockalingam, MD FRCPC
Sub-Investigator: Johane Allard, MD FRCPC
Sub-Investigator: Ivan G Fantus, MD FRCPC

Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Elizabeth J Heathcote, MD FRCPC (University Health Network, Toronto)

More Information

Responsible Party: University Health Network ( Dr E Jenny Heathcote )
Study ID Numbers: 08-0545-AE
Study First Received: September 17, 2008
Last Updated: January 22, 2009
ClinicalTrials.gov Identifier: NCT00755742
Health Authority: Canada: Ethics Review Committee

ClinicalTrials.gov processed this record on March 06, 2009