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A Pilot Trial to Evaluate the Effect of Diet and Exercise in Renal Transplant Recipients on Tacrolimus

Phase 4
Completed
Conditions
Kidney Transplantion
Renal Transplantion
Interventions
Registration Number
NCT00492661
Lead Sponsor
Janssen-Cilag Pty Ltd
Brief Summary

The purpose of this trial is to investigate whether a combined dietary and exercise intervention, added to standard care, reduces the expected frequency of insulin resistance in renal (kidney) transplant recipients on tacrolimus.

Detailed Description

This is an open-label (all people know the identity of the intervention), prospective (study following participants forward in time), single-arm, multi-center (conducted in more than 1 center), interventional pilot study of the effects of a combined dietary and exercise intervention on glucose metabolism. The duration of this study will be 6 months and will include following visits: Baseline, Week 4, Week 12, and Week 24. Dietary compliance will be evaluated with a 3-day food record and during weekly telephone conversations and face-to-face visits with a dietician. Exercise compliance will be measured using an exercise log presented to the co-ordinator at the end of each month. Primarily, participants with insulin resistance will be assessed by Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) of greater than 1 at 6 months. Participants' safety and tolerability will be monitored throughout the study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
55
Inclusion Criteria
  • Participants who has sufficiently recovered from surgery to tolerate an intensive exercise evaluation
  • Participants who have received a living-donor or cadaveric (from dead donor) renal transplant
  • Participants who has been initiated tacrolimus as first-line immunosuppressive agent
  • Participants who has given informed consent forms
Exclusion Criteria
  • Participants with significant disease or disability that prevents taking part in a diet or exercise regime (e.g. cardiac instability, including unstable angina [chest pain due to decreased oxygen being supplied to the heart] and/or other unstable disease, severe cognitive [mental functioning] impairment)
  • Participants with significant post-surgical complications that prevent participation in the exercise component of the study (e.g. wound dehiscence [pathologic process consisting of a partial or complete disruption of the layers of a surgical wound] or infection)
  • Participants with contraindications to maximal exercise testing or high-intensity progressive resistance training (e.g. proliferative diabetic or hypertensive retinopathy, un-repaired aneurysm, critical aortic stenosis, recurrent symptomatic hernias, New York Heart Association (NYHA) class-IV congestive heart failure)
  • Participants with non-ambulatory (mobility) status
  • Participants who require ongoing systemic immunosuppressive therapy for an indication other than renal transplant and this therapy is higher than that required for their kidney disease

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Tacrolimus With Diet and Exercise InterventionTacrolimus With Diet and Exercise InterventionParticipants on tacrolimus for immunosuppression (drug which suppresses the body's immune response, used in transplantation and diseases caused by disordered immunity) will be provided with intensive dietary advice and supervised progressive resistance training (PRT) for a period of 6 months. Dosage and administration of tacrolimus will be as per Investigator's discretion.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Insulin ResistanceWeek 24

Percentage of participants with insulin resistance as defined by a Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) greater than 1. HOMA uses fasting glucose and insulin (or C-peptide) to assess beta-cell function and IR. HOMA-IR is used to estimate insulin resistance. HOMA-IR is calculated by equation: HOMA-IR=fasting plasma insulin (milliunit \[mU\] per liter \[L\]) \* fasting plasma glucose (millimole per liter \[mmol per L\]) divided by 22.5.

Secondary Outcome Measures
NameTimeMethod
Body Composition: Percent Body FatBaseline and Week 24

Body fat will be assessed by DEXA scan.

Percentage of Participants With Impaired Fasting Glycaemia (IFG)Week 24

IFG is defined as a fasting venous plasma glucose concentration greater than or equal to 6.1 mmol per L but less than 7.0 mmol per L, together with a 2-hour plasma glucose concentration of less than 7.8 mmol per L.

Bone Mineral DensityBaseline and Week 24

Bone mineral density is measured by Dual-Energy X-ray Absorptiometry (DEXA).

Percentage of Participants With Impaired Glucose Tolerance (IGT)Week 24

IGT is defined as fasting venous plasma glucose of less than 7.0 mmol per L, together with a 2-hour plasma glucose of greater than or equal to 7.8 mmol per L but less than 11.1 mmol per L.

Beta Cell FunctionBaseline, Week 4, Week 12, and Week 24

HOMA-Beta is used to assess beta-cell function. HOMA-Beta is a measure of Beta-cell function (higher values present increased insulin secretion for a given glucose level). HOMA-Beta is calculated by the equation: HOMA-Beta=(20\*FPI) divided by (FPG-3.5), where, FPI is fasting plasma insulin concentration (mU per L) and FPG is fasting plasma glucose concentration (mmol per L).

Hemoglobin A, Glycosylated (HbA1c)Baseline, Week 4, Week 12 and Week 24

Measurement of the change in HbA1c will be performed in fasted state and in local laboratories.

Percentage of Participants Compliant With Both Dietary Advice and Exercise Program and Non-Compliant With Dietary Advice or Exercise ProgramWeek 4, Week 12 and Week 24

Compliance with dietary advice will be measured on a categorical scale ranging from 0=no compliance to 10=full compliance. Compliance with exercise program is measured as the completion of 3 exercise sessions per week for the 6-month period.

Percentage of Participants With Diabetes Mellitus (DM)Week 24

DM is defined as a fasting plasma glucose concentration greater than or equal to 7.0 mmol per L, or a 2-hour plasma glucose greater than or equal to 11.1 mmol per L.

Body Composition: Lean Mass, Bone Mass and Adjusted WeightBaseline and Week 24

Body composition lean mass and bone mass will be assessed by DEXA scan.

36-Item Short-Form (SF-36) Score - Health SurveyBaseline, Week 12 and Week 24

This SF-36 standardize survey evaluates participants health by 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as Physical Component Scores (PCS) and Mental Component Scores (MCS). The score for a section is an average of the individual question scores, which are scaled 0 to 100, Higher score indicates highest level of functioning.

Number of Participants With Acute Rejection, Graft Loss and DeathWeek 24

Acute rejection episodes are classified into: Spontaneously resolving - a rejection episode which is not treated with new or increased corticosteroid medication, antibodies or any other medication. Corticosteroid sensitive - a rejection episode, which is treated with new or increased corticosteroid medication only. Corticosteroid resistant - a rejection episode, which is not resolve following treatment with corticosteroids. Graft loss is defined as re-transplantation, nephrectomy, death or as dialysis ongoing at study end (or at withdrawal of the participants from the study).

Body Mass Index (BMI)Baseline, Week 4, Week 12 and Week 24

BMI is a statistical measurement which compares a person's weight and height. Though it does not actually measure the percentage of body fat, it is used to estimate a healthy body weight based on participant's height. BMI is equal to weight divided by height square. Weight is measured in Kilogram and height is measured in meter.

Blood Pressure: Systolic and Diastolic PressureBaseline, Week 4, Week 12 and Week 24

Measurement of blood pressure will be performed by using a completely automated device consisting of an inflatable cuff and oscillatory detection system. Blood pressure will be taken supine, after 5 minutes of rest.

Lipid ProfileBaseline, Week 4, Week 12, and Week 24

In lipid profile total cholesterol, high-density lipoprotein (HDL) - cholesterol, low-density lipoprotein (LDL) - cholesterol and triglycerides levels will be evaluated. Measurement of the lipid profile will be performed in fasted state.

Body Composition: T Score (Full Body) and Z Score (Full Body)Baseline and Week 24

Body composition: T score (Full body) and Z score (full body) will be assessed by DEXA scan.

Estimated Glomerular Filtration Rate (eGFR)Baseline, Week 4, Week 12 and Week 24

The eGFR is calculated by Modification of Diet in Renal Disease (MDRD) equation is recommended by Kidney Health Australia as the calculation of choice for predicting GFR. According to MDRD equation eGFR is equal to 186\*(Serum creatinine/0.095)\^-1.154\*age\^0.203\*race\*sex, where the unit of serum creatinine is micro mole per L, the age is in years; race is 1.212 if African American, or 1 otherwise; and sex equals 1 if male, and 0.742 if female. eGFR will be compared against baseline.

Percentage of Participants who will be Sedentary, Insufficiently Active and Sufficiently Active According to Active Australia Survey (AAS)Week 4, Week 12 and Week 24

AAS is used for physical activity surveillance and it consists of following categories: 'sedentary' - people who are doing no activity at all; 'sufficiently active'- participation in at least 150 minutes per week; 'insufficiently active'- the remainder participants whose participation is not enough to obtain a health benefit.

Waist to Hip Ratio (WHR)Baseline, Week 4, Week 12 and Week 24

WHR is performed using a standard medical measuring tape, with recordings documented in centimeters. Measurements will be compared against data from participating sites (where available) and against baseline. Measurement of hip circumference will be performed at the widest part of the buttocks. Measurement of the waist will be performed at the smaller circumference of the natural waist (usually just superior to the umbilicus). WHR is calculated by dividing the waist measurement by the hip measurement, and recorded to 2 decimal places.

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