Trial from ANZCTR


Trial ID ACTRN12610000497000
Trial Status: Registered
Date Submitted: 12/06/2010
Date Registered: 16/06/2010
Prospectively registered

Page 1

Public title Weight management and Atrial Fibrillation: The impact of weight and risk factor management on AF burden in overweight and obese patients.
Update:
 
Reason:
 
Study title in 'Participant- Intervention- Comparator- Outcome (PICO)' format Impact of a weight and risk factor management program in overweight and obese patients, on atrial fibrillation burden.
Update:
 
Reason:
 
Secondary ID [1] 251997 0
090817
Update:
 
Reason:
 
UTN Nil
Update:
 
Reason:
 
Trial acronym Nil
Update:
 

Page 2

Health condition(s) or problem(s) studied:
Obesity 257561 0
 Update:
 Reason:
Atrial arrhythmias 257562 0
 Update:
 Reason:
Condition category: Condition code:
Diet and nutrition Obesity
 Update:
 Update:
  Reason:
257718 257718 0 0
Cardiovascular Other cardiovascular diseases
 Update:
 Update:
  Reason:
257719 257719 0 0

Page 3

Descriptions of intervention(s) / exposure The Weight Management and Atrial Fibrillation is a multi-component prospective study aimed at investigating multiple research questions pertinent to obesity and atrial fibrillation:
1. The impact of weight and risk factor management on AF burden in overweight and obese patients
2. The impact of weight reduction prior to AF catheter ablation on procedure outcomes, in overweight and obese patients
3. The impact of weight reduction on the AF substrate and autonomic system modulation in overweight and obese patients: A mechanistic study (separate registration)

Weight Management and Atrial Fibrillation: The impact of weight and risk factor management on AF burden in overweight and obese patients.
Patients in the intervention group undergo a 2 phase physician-led weight management program concurrently with tight metabolic risk factor control.
Upon randomization to the intervention arm, patients undergo a 2 month modified very low calorie diet (VLCD) and a gradually titrated low intensity exercise program.
During the high intensity modified VLCD phase, patients will be prescribed a standard nutritionally complete meal replacement product (Prima Health Solutions, Kickstart) for 2 of the 3 daily meals. This will be ongoing for 2 months and used in conjunction with a didactic eating plan framework. Generally, patients will be prescribed an eating plan focusing on:
1. Calorie maintenance 800-1200 calories/day
2. Low glycemic index foods
3. High mono and poly unsaturated fats based foods
4. Low saturated fats, cholesterol and sodium based foods
5. Alcohol reduction (less than or equal to 30g/week)
Patients will be required to maintain a lifestyle journal outlining:
1. Exercise (duration and type)
2. Food intake (quantity and type)
3. Blood pressure measurements
Physical activity prescription is tailored as follows:
1. Initially 3 x 20 minute sessions of low intensity exercise per week (usually walking)
2. This is titrated upwards over the initial 2 months to 1 – 2 low intensity session(s) plus 1 – 2 moderate intensity session(s) per week. Moderate intensity sessions include, jogging, brisk walking, swimming, cross-trainer, rowing machine, cycling
3. In the case of limiting musculoskeletal conditions, hydrotherapy or aqua aerobics are utilized instead
4. Patients are encouraged to utilize pedometers to quantify their personal best and to aim to supersede this over time
At commencement, they are issued with pre-specified written material on healthy eating, dining out, food shopping and physical activity. During the initial phase of the program, patients will be reviewed monthly in a specialized weight and risk factor management clinic along with their lifestyle journal. Following the 2 month high intensity phase, patients will undergo a more gradual weight management program with greater focus on permanent lifestyle change. During the second phase of the study, meal replacement sachets will be discontinued. Patients will be reviewed 3 monthly in the clinic for the remaining duration of follow-up (15-months).
At baseline, weight, body mass index (BMI), waist circumference (WC), height, blood pressure as well as baseline demographic data are recorded. Patients have blood drawn for baseline fasting biochemistry (BUN, LFTs, INR, hsCRP, TSH, T4, Insulin, Glucose, Cholesterol, HDL, LDL and triglycerides). All patients undergo stringent risk factor identification and management. In addition to weight, metabolic risk factors include:
1. Smoking
2. Hyperlipidemia
3. Hypertension
4. Glucose intolerance or diabetes mellitus
5. Alcohol intake
6. Obstructive sleep apnea
All patients undergo sleep apnea screening through overnight polysommnography at a dedicated sleep unit. When clinically indicated (in conjunction with AHI interpretation), CPAP may be prescribed and titrated.
Patients are educated about tobacco and alcohol harm and provided with written education. Follow-up and feedback is provided on clinic visits. Alcohol reduction to less than or equal to 30g/week is aimed for, in view of established metabolic disease and cardiac arrhythmia.
In the event of intermediate fasting glycemia, a 2 hour glucose tolerance test is undertaken. If glucose intolerant or insulin resistant continued lifestyle measures are pursued. Patients with frank diabetes are prescribed oral hypoglycemic agents and referred to a diabetes clinic.
Hypertension is diagnosed based on family physician records and documented readings in the lifestyle journal. Management with a combination of lifestyle measures, salt reduction and pharmacotherapy is undertaken. Medication may be combined and titrated based on clinician judgment and patient tolerance.
During the follow-up visits, patients will undergo face-to-face counseling and feedback based on anthropometric measures and lifestyle journal. Patients will have access to 24 hour email and telephone support in addition to additional counseling sessions if required. At each appointment, data is entered into the OBEMAN software program.
Periodic measurements include:
1. BMI, WC, blood pressure, 12-lead ECG (baseline and three monthly)
2. Anti-hypertensive and anti-arrhythmic medication usage (baseline and three monthly)
3. Atrial Fibrillation Severity Scale (AFSS) (baseline and 3, 9, 12 and 15 months)
4. 7 day Holter recording (baseline and 15 months)
5. Transthoracic echocardiography (baseline and 15 months)
6. Cardiac MRI (baseline and 15 months)
7. Fasting plasma biochemistry (baseline and 15 months)
Weight Management and Atrial Fibrillation: The impact of weight reduction and risk factor management prior to AF catheter ablation on procedure outcomes, in overweight and obese patients.
The aim of this sub-study is to determine the impact of weight and risk factor management prior to catheter ablation on procedure outcomes, in overweight and obese subjects.
Patients who have undergone weight and risk factor modification and are clinical candidates for catheter ablation are recruited into this arm of the study.
Patients undergo the weight and risk factor management program as per the protocol in the sub-study, “Weight Management and Atrial Fibrillation: The impact of weight and risk factor management on AF burden in overweight and obese patients” (above). Patients who attain either end-point:
1. BMI < 27 and/or WC < 100cm (males) [<90cm (females)]
2. 15 month follow-up
Patients who remain symptomatic of AF are eligible to undergo a catheter ablation. Following the catheter ablation procedure, patients continue to undergo weight and risk factor management with three monthly follow-up for 24 months post procedure. The recurrence of AF post ablation is determined on follow-up.
Periodic measurements following catheter ablation include:
1. BMI, WC, blood pressure, 12-lead ECG (baseline and three monthly following procedure, for 24 months)
2. Anti-hypertensive and anti-arrhythmic medication usage (baseline and three monthly following procedure, for 24 months)
3. Atrial Fibrillation Severity Scale (AFSS) (three monthly following procedure, for 24 months)
4. 7 day Holter recording (baseline and 24 months)
5. Transthoracic echocardiography (baseline and 24 months)
6. Cardiac MRI (baseline and 24 months)
7. Fasting plasma biochemistry (baseline and 24 months)

Weight Management and Atrial Fibrillation: The impact of weight reduction on the AF substrate and autonomic system modulation in overweight and obese patients: A mechanistic study.
This study will be registered separately. It is mentioned briefly outlined here due to its overlapping nature and common steering committee.
The aim of this sub-study is to investigate the changes in the autonomic system and arrhythmogenic substrate with weight reduction, and the effect this has on AF burden.
Patients who have undergone weight and risk factor modification as per protocol for the sub-study, “Weight Management and Atrial Fibrillation: The impact of weight and risk factor management on AF burden in overweight and obese patients” (above), are eligible for entry into this sub-study.
The aim of this sub-study is to determine the changes in autonomic tone and AF substrate with weight and risk factor management.
The periodicity of follow-up data recording is as follows:
1. BMI, WC, blood pressure, 12-lead ECG (baseline and three monthly)
2. Anti-hypertensive and anti-arrhythmic medication usage (baseline and three monthly)
3. Atrial Fibrillation Severity Scale (AFSS) (baseline and 3, 9, 12 and 15 months)
4. 7 day Holter recording (baseline and 15 months)
5. Heart rate variability (baseline and 15 months)
6. Exercise stress testing (baseline and 15 months)
7. Head up tilt table testing (baseline and 15 months)
8. Transthoracic echocardiography (baseline and 15 months)
9. Delayed enhancement Cardiac MRI (baseline and 15 months)
10. Fasting plasma biochemistry (baseline and 15 months)

Control/comparator group:
Standard care is provided for the control group. This consists of:
1. Written material and verbal advice through direct contact counseling
2. 3g/day of marine omega triglycerides (docosahexaenoic acid and eicosapenteanoic acid)
3. Scheduled 3 monthly clinic visits
As for the intervention arm, patients are required to maintain a lifestyle journal which is reviewed three monthly. Diet and exercise counseling is provided via written material as a once-off session at commencement of participation.
Risk factors identification, management and data recording is carried out as per the intervention group.
Update:
 
Reason:
 
Intervention Code:
Prevention 256646 0
Update:
 
Reason:
 
Intervention Code:
Treatment: surgery 256647 0
Update:
 
Reason:
 
Intervention Code:
Diagnosis 256648 0
Update:
 
Reason:
 
Intervention Code:
Lifestyle 284904 0
Update:
 
Reason:
 
Comparator / control treatment Standard care is provided for the control group. This consists of:
1. Written material and verbal advice through direct contact counseling
2. 3g/day of marine omega triglycerides (docosahexaenoic acid and eicosapenteanoic acid)
3. Scheduled 3 monthly clinic visits
As for the intervention arm, patients are required to maintain a lifestyle journal which is reviewed three monthly. Diet and exercise counseling is provided via written material as a once-off session at commencement of participation.
Risk factors identification, management and data recording is carried out as per the intervention group.
Update:
 
Reason:
 
Control group Active
Update:
 
Reason:
 

Page 4

Primary Outcome: Atrial arrhythmia burden and freedom from atrial fibrillation. Requirement for an ablation procedure or relapse into AF following an ablation. This is done using validated AF-specific questonnaires, Holter monitoring and 12 lead- electrocardiograph (ECG) recordings. 258620 0
Update:
 
Reason:
 
Timepoint: Baseline, 3, 6, 9, 12 and 15 month follow-up 258620 0
Update:
 
Reason:
 
Primary Outcome: Cardiac structure and function on echocardiography and doppler echocardiography. 258621 0
Update:
 
Reason:
 
Timepoint: Baseline and 15 months 258621 0
Update:
 
Reason:
 
Secondary Outcome: Atrial ectopy burden. This will be assessed by continuous 7-day Holter monitoring. 264529 0
Update:
 
Reason:
 
Timepoint: Baseline 15 months and 24 months. 264529 0
Update:
 
Reason:
 
Secondary Outcome: Non-invasive and invasive assessment of the atrial arrhythmic substrate. Atrial voltage maps and conduction velocity. 264556 0
Update:
 
Reason:
 
Timepoint: Baseline only, according to body mass index. 264556 0
Update:
 
Reason:
 
Secondary Outcome: Serum fasting biochemistry 297557 0
Update:
 
Reason:
 
Timepoint: Baseline and follow-up (15 months) 297557 0
Update:
 
Reason:
 
Secondary Outcome: Cardiac structure and function. Delayed-enhancement atrial scar burden. This will be performed using cardiac magnetic resonance imaging (CMR) with delayed contrast enhancement. 297558 0
Update:
 
Reason:
 
Timepoint: Baseline and 15 months. 297558 0
Update:
 
Reason:
 

Page 5

Key inclusion criteria Inclusion criteria were: symptomatic paroxysmal or persistent AF; BMI (kgm-1)>27; waist circumference (cm) >100 (male) or >90 (females); and age 21-75 years.
Update:
 
Reason:
 
Minimum age 21 Years
Update:
 
Reason:
 
Update:
 
Reason:
 
Maximum age 75 Years
Update:
 
Reason:
 
Update:
 
Reason:
 
Gender Both males and females
Update:
 
Reason:
 
Healthy volunteers? No
Update:
 
Reason:
 
Key exclusion criteria Inability to give informed consent, significant (moderate-severe) valvular heart disease, moderate-severe left ventricular systolic dysfunction/moderate-severe cardiomyopathy, renal impairment, significant gastrointestinal/mal-absorptive disorder, vitamin and trace element deficiency, insulin-dependent diabetes mellitus, uncontrolled underlying significant medical condition, unstable INR, significant endocrinopathy and recent participation (3 months) in a structured weight loss program.
Update:
 
Reason:
 

Page 6

Study type Interventional
Update:
 
Reason:
 
Purpose of the study Treatment
Update:
 
Allocation to intervention Randomised controlled trial
Update:
 
Reason:
 
Describe the procedure for enrolling a subject and allocating the treatment (allocation concealment procedures) Allocation concealment using unscreened referral of all subjects meeting above inclusion criteria. Allocation involved contacting the holder of the allocation schedule who was "off site"or at a central administration site.
Update:
 
Reason:
 
Describe the methods used to generate the sequence in which subjects will be randomised (sequence generation) Randomization between 0 (control) and 1 (active) using an electronic random number generator.
Update:
 
Reason:
 
Masking / blinding Open (masking not used)
Update:
 
Reason:
 
Who is / are masked / blinded (choose all that apply)


Update:
       
Reason:
 
Assignment Parallel
Update:
 
Reason:
 
Other design features Follow-up at 15 months.
Update:
 
Reason:
 
Type of endpoint(s) Efficacy
Update:
 
Reason:
 
Statistical Methods/Analysis
Update:
 
Reason:
 

Page 7

Phase Not Applicable
Update:
 
Reason:
 
Anticipated date of first participant enrolment 30/06/2010
Update:
 
Reason:
 
Date of first participant enrolment
Update:
 
Reason:
 
Anticipated date last participant recruited/enrolled
Update:
 
Reason:
 
Actual date last participant recruited/enrolled
Update:
 
Reason:
 
Target sample size 800
Update:
 
Reason:
 
Recruitment status Closed: follow-up complete
Update:
 
Reason:
 

Recruitment in Australia

Recruitment state(s)
Update:
 
Reason:
 
Postcode: 5000 2990 0
Update:
 
Reason:
 
Postcode: 5117 2991 0
Update:
 
Reason:
 
Postcode: 5012 2992 0
Update:
 
Reason:
 
Postcode: 5009 2993 0
Update:
 
Reason:
 
Postcode: 5014 2994 0
Update:
 
Reason:
 
Postcode: 5154 2995 0
Update:
 
Reason:
 
Postcode: 5100 2996 0
Update:
 
Reason:
 
Postcode: 5200 2997 0
Update:
 
Reason:
 
Postcode: 5300 2998 0
Update:
 
Reason:
 
Postcode: 5400 2999 0
Update:
 
Reason:
 
Postcode: 5500 3000 0
Update:
 
Reason:
 

Recruitment outside Australia

Page 8

Funding Source: University 257130 0
Update:
 
Reason:
 
Name: The university of Adelaide 257130 0
Update:
 
Reason:
 
Address: The University of Adelaide
North Terrace, Adelaide, SA 5000
257130 0
Update:
 
Reason:
 
Country: Australia 257130 0
Update:
 
Reason:
 
Funding Source: Hospital 257131 0
Update:
 
Reason:
 
Name: The Royal Adelaide Hospital 257131 0
Update:
 
Reason:
 
Address: The Royal Adelaide Hospital
North Terrace, Adelaide, SA, 5000
257131 0
Update:
 
Reason:
 
Country: Australia 257131 0
Update:
 
Reason:
 
Primary Sponsor University
Update:
 
Reason:
 
Name: The University of Adelaide
Update:
 
Reason:
 
Address: The University ofAdelaide
north Terrace, Adelaide, SA 5000
Update:
 
Reason:
 
Country: Australia
Update:
 
Reason:
 
Secondary Sponsor: Hospital 256388 0
Update:
 
Reason:
 
Name: The Royal Adelaide Hospital 256388 0
Update:
 
Reason:
 
Address: The Royal Adelaide Hospital
North Terrace, Adelaide, SA, 5000
256388 0
Update:
 
Reason:
 
Country: Australia 256388 0
Update:
 
Reason:
 

Page 9

Has the study received approval from at least one Ethics Committee? Yes
Update:
 
Reason:
 
Ethics Committee name: The Royal Adelaide Hospital, Research Ethics Committee 259169 0
Update:
 
Reason:
 
Address: The Royal Adelaide Hospital
North Terrace, Adelaide, SA, 5000
259169 0
Update:
 
Reason:
 
Country: Australia 259169 0
Update:
 
Reason:
 
Approval Date: 27/10/2009 259169 0
Update:
 
Reason:
 
Submitted Date: 01/08/2009 259169 0
Update:
 
Reason:
 
HREC: 090817a 259169 0
Update:
 
Reason:
 
Brief summary The purpose of the study is to evaluate the impact of a structured weight managment program as part of the management of atrial fibrillation. It is also intended to assess the effect of weight reduction on the efficacy of atrial fibrillation following catheter ablation and the effect of weight and risk factor management on autonomic tone/pro-arrhythmic substrate.
Update:
 
Reason:
 
Trial website
Update:
 
Trial related presentations / publications
Update:
 
Public Notes
Update:
 

Page 10

Principal Investigator
Title:
Update:
 
Reason:
 
31283 0
Name:
Update:
 
Reason:
 
31283 0
Address:
Update:
 
Reason:
 
31283 0
Country:
Update:
 
31283 0
Reason:
 
Tel:
Update:
 
Reason:
 
31283 0
Fax:
Update:
 
Reason:
 
31283 0
Email:
Update:
 
Reason:
 
31283 0
Contact person for public queries
Title:
Update:
 
Reason:
 
14530 0
Name: Professor Prash Sanders
Update:
 
Reason:
 
14530 0
Address: Cardiovascular Research Centre. Level 5 McEwin Building The Royal Adelaide Hospital North Terrace, Adelaide, SA, 5000
Update:
 
Reason:
 
14530 0
Country: Australia
Update:
 
14530 0
Reason:
 
Tel: +61 8 82222723
Update:
 
Reason:
 
14530 0
Fax: +61 8 82222722
Update:
 
Reason:
 
14530 0
Email: prash.sanders@adelaide.edu.au
Update:
 
Reason:
 
14530 0

Contact person for scientific queries
Title:
Update:
 
Reason:
 
5458 0
Name: Dr. Hany Abed
Update:
 
Reason:
 
5458 0
Address: Cardiovascular Research Centre. Level 5 McEwin Building The Royal Adelaide Hospital North Terrace, Adelaide, SA, 5000
Update:
 
Reason:
 
5458 0
Country: Australia
Update:
 
5458 0
Reason:
 
Tel: +61 8 82222723
Update:
 
Reason:
 
5458 0
Fax: +61 8 82222722
Update:
 
Reason:
 
5458 0
Email: hany.abed@adelaide.edu.au
Update:
 
Reason:
 
5458 0

Contact person responsible for updating information
Title:
Update:
 
Reason:
 
23602 0
Name: Dr. Hany Abed
Update:
 
Reason:
 
23602 0
Address: Cardiovascular Research Centre. Level 5 McEwin Building The Royal Adelaide Hospital North Terrace, Adelaide, SA, 5000
Update:
 
Reason:
 
23602 0
Country: Australia
Update:
 
23602 0
Reason:
 
Tel: +61 8 82222723
Update:
 
Reason:
 
23602 0
Fax: +61 8 82222722
Update:
 
Reason:
 
23602 0
Email: hany.abed@adelaide.edu.au
Update:
 
Reason:
 
23602 0
   

Addition Cancer fields
Update:
 
Reason:
 
Update:
 
Reason:
 
Update:
 
Reason:
 
Update:
 
Reason:
 
Update:
 
Reason:
 
Update:
 
Reason: