Contact information
Type
Scientific
Primary contact
Prof Nicholas Finer
ORCID ID
Contact details
University College London Hospitals
Division of Bariatric Medicine and Surgery
3rd Floor Central Wing
250 Euston Road
London
NW1 2PQ
United Kingdom
+44 0845 1555000 ext 4962
n.finer@ucl.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N0544174250
Study information
Scientific title
Acronym
Study hypothesis
What is the effect of weight loss and weight loss maintenance on heart function (cardiac reserve) in obese heart failure patients? We aim to investigate heart function and cardiac reserve (the ability of the heart to respond to exercise) before and after therapeutic weight loss in obese patients with mild to moderate heart failure.
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Nutritional, Metabolic, Endocrine: Obesity
Intervention
This is a randomised controlled study of intensive diet with weight loss against non-intervention in obese patients with heart failure. The non-intervention group is included to provide information on the background progression or regression of heart failure without weight loss and in the situation where it is not possible to provide a placebo weight loss diet. Patients will be informed that they may be randomised to this control group and will not be receiving a therapeutic intervention. Since the study is designed to assess the benefit (or harm) of weight loss, it is ethically appropriate for such a non-intervention control group. Since it seems unlikely that there will be significant changes in cardiac function in the non-intervention group over the study period of 16 weeks, randomisation will be 3:1.
The main study has been powered on the basis of published data. The power calculations are estimated on the basis of the difference in peak vO2 measurements. Assuming a peak oxygen utilisation (VO2) during exercise of 19 (SD 3.9) ml/kg/min 24 subjects will be required to detect a 10% improvement in peak VO2 after weight loss with a p value of <0.05, power 85%). A pilot study in 6 patients (non-randomised, and receiving the intensive diet intervention) will be undertaken before the main study and will be used to provide information to confirm (or alter) the power calculations.
Obese patients with heart failure will be recruited from the cardiology clinic at Addenbrookes hospital. Subjects will be given information leaflets about the study so that they can read and discuss them at home prior to giving consent at a later date (>48 hours). After an initial screening visit, at which patients will give informed consent, measurements will be made of peak VO2, blood parameters, and heart function. Based on these results, patients will be informed whether or not they meet the inclusion/exclusion criteria. If they do, at the subsequent visit (measurement baseline) they will be randomised to the active intervention or control group. They will be randomised to either intensive dietary intervention (intervention group) or observation (control group). Both groups will therefore attend one screening visit, and 3 measurement visits (week 0, 6 and 16). The active intervention group will also attend for weekly and then two-weekly interim visits so that their diet can be monitored and managed. The control group will make only one interim visit at week 10.
Subjects will attend the Clinical Research Facility (CRF) at Addenbrookes Hospital Centre for Clinical Investigation (ACCI) at 9am on the study day. Subjects will stay overnight (i.e. for 36 hours) and all measurements listed will be performed during the stay in the CRF. These are: peak VO2 during supervised exercise on a treadmill, measurements of left ventricular function by either echocardiography or MRI, heart rate variability using standard electronic recording devices, body composition using standard techniques, plasma BNP levels and other blood measures, quality of life measurement by standard questionnaire, and spontaneous physical activity using a commercially available recording device.
A low calorie liquid diet will be provided to the intervention group. This dietary regimen is routinely used to achieve initial weight loss by specialists at weight loss management clinics worldwide and also in the Obesity Clinic at Addenbrookes Hospital. Patients will continue this diet for 6 weeks with regular weekly interim follow up. This will be followed by weight loss maintenance diet, the energy value of which will be calculated from standard equation relating height, weight and age to basal metabolic rate.
This study design will allow us to separate effects from acute weight loss and a stable lowered body weight.
The study has been designed with consultation and involvement of experts in obesity, cardiology, and nutrition. The diet intervention is informed by many years experience, including patient feedback and audit, from the setting of an NHS obesity clinic and other clinical trials. For this reason patient involvement in the design of this study was deemed unnecessary.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measure
Peak oxygen consumption during cardiopulmonary exercise testing (Peak VO2) following acute weight loss (week 6) and weight loss maintenance phase(16 weeks)
Secondary outcome measures
Not provided at time of registration
Overall trial start date
01/03/2006
Overall trial end date
28/02/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
38 patients. Pilot study: 6 patients will be recruited for active dietary intervention. Main study: 24 patients will be recruited for the active dietary intervention and 8 patients for the control.
Inclusion criteria:
1. Obese patients defined at body mass index (BMI) of above 30 and <40 kg/m2 (excessive body weight will preclude exercise and accurate imaging)
2. Stable heart failure patients of NHYA (New York Heart Association) class II or III (patients must be able to undertake exercise testing). Diagnosis of heart failure will be based on standard criteria of symptoms of more than 6 months with confirmed LVEF impairment on echocardiogram
3. Age above 25 and below 70 years (to ensure patients can participate with the exercise etc)
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
38
Participant exclusion criteria
1. Unable to give informed consent
2. Subjects with renal impairment defined by creatinine >170 Μmol/l (inappropriate to include patients with more complex
illness in this study).
3. Patients with Diabetes Mellitus on antidiabetic medication (other
than metformin - diet and weight loss would require alteration of insulin or non-metformin diabetes treatment, complicating assessments)
4. Heart failure patients of NHYA (New York Heart Association) class <II or >III (patients must be able to undertake exercise testing)
Recruitment start date
01/03/2006
Recruitment end date
28/02/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University College London Hospitals
London
NW1 2PQ
United Kingdom
Sponsor information
Organisation
Record Provided by the NHSTCT Register - 2006 Update - Department of Health
Sponsor details
The Department of Health
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)20 7307 2622
dhmail@doh.gsi.org.uk
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Cambridge Consortium - Addenbrooke's (UK) Own Account
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2008 abstract: Effects of Rapid Weight Loss and Short-Term Weight Loss Maintenance in Obese Patients with Cardiovascular Risks and/or Heart Failure: a Pilot Study. Myint, KS; Northcott, S; Heck, P; Wright, A;Murgatroyd, P; Dutka, D; Brown, M;Ashby, M; Dhatariya, K; Finer, N. Obesity 16, S155. As part of poster session published in http://www.nature.com/oby/journal/v16/n1s/pdf/oby2008375a.pdf (page 59/86)