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LOSE-AF: Can Weight Loss Help Patients With Atrial Fibrillation? (LOSE-AF)

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ClinicalTrials.gov Identifier: NCT03713775
Recruitment Status : Recruiting
First Posted : October 22, 2018
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
University of Oxford

Brief Summary:

Background Atrial fibrillation (AF) affects over 1 million individuals in the UK and results in costs of over £450 million per year to the National Health Service (NHS). Current rhythm control strategies are limited by high recurrences of AF. New strategies tackling more upstream pathophysiological mechanisms are most needed. The incidence and prevalence of AF markedly increase with age, whilst obesity is the strongest modifiable risk factor for AF. Preliminary data in relatively young patients suggest that weight loss programmes may reduce AF burden and improve AF-related symptoms. Such programmes could be a widely-applicable and cost-effective option in AF management if they are also effective in elderly patients with AF, particularly if they also improve physical performance.

Aim The aim of this study is to investigate whether, in older overweight/obese AF patients, referral to a weight loss programme with meal replacement & behavioral support can reduce AF-recurrences and improve physical performance compared to usual care.

Study design Parallel-group, open-label, multi-centre randomised controlled trial. Elderly individuals (60-85 years) with persistent AF and elevated body mass index (BMI; ≥ 27 kg/m2) will be recruited. Participants will be randomly allocated (1:1) to (a) referral to a meal replacement programme with behavioral support (intervention) or (b) usual care (control) for 32-to-36 weeks. The primary endpoints are AF recurrence and physical performance test (PPT) score. Participants randomised to the study intervention will be referred to a commercial provider (CP) providing the intervention. The co-primary endpoints of AF recurrence & PPT score will be analysed irrespective of compliance during the scheduled treatment period following an intention-to-treat principle.


Condition or disease Intervention/treatment Phase
Atrial Fibrillation Overweight and Obesity Other: Meal Replacement Weight Loss Programme Other: Usual Care Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: This is an open-label randomised controlled study and patients will be aware of their treatment allocation. Potentially subjective measurements will be undertaken by observers blinded to treatment allocation; in particular, all imaging and ECG monitoring data will be anonymised prior to post-processing, and PPT score will be assessed by a research nurse blinded to treatment allocation. All study assessments will be coded and recorded blinded to treatment allocation.
Primary Purpose: Treatment
Official Title: Weight Loss in Elderly Patients With Atrial Fibrillation (LOSE-AF): A Randomised Controlled Trial
Actual Study Start Date : November 14, 2018
Estimated Primary Completion Date : October 1, 2021
Estimated Study Completion Date : October 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Meal Replacement Weight Loss Programme
The study intervention will be the referral to a commercial provider (CP) offering a Meal Replacement Weight Loss Programme with behavioural support. Briefly, participants will be referred to a nominated CP local counsellor who will set regular appointments during a period of 32-to-36 weeks to provide behavioural support, weight monitoring, and deliver formula meals. All counsellors delivering the programme will receive, beyond their routine training and accreditation, specific information related to this study before being allocated patients. The programme conventionally includes the 3 phases (meal replacement phase, transition phase, and weight maintenance phase) but the Consultant will have full discretion to modify and tailor this programme to suit each individual participant.
Other: Meal Replacement Weight Loss Programme
The study intervention will be the referral to a commercial provider (CP) offering a Meal Replacement Programme. Briefly, participants will be referred to a nominated CP local counsellor who will set regular appointments during a period of 32-to-36 weeks to provide behavioural support, weight monitoring, and deliver formula meals. All counselors delivering the programme will receive, beyond their routine training and accreditation, specific information related to this study before being allocated patients.

Active Comparator: Usual Care
Participants randomised to the control group will receive best usual care, consisting of a one-off face-to-face consultation on weight loss with a nurse at baseline (~15 min at the John Radcliffe Hospital, Oxford) together with supporting written information (i.e. a copy of the booklet 'Facts not fads - Your simple guide to healthy weight loss.')
Other: Usual Care
Participants randomised to the control group will receive best usual care, consisting of a one-off face-to-face consultation on weight loss with a nurse at baseline (~15 min), together with supporting written information.




Primary Outcome Measures :
  1. AF recurrence (%) [ Time Frame: 8 months ]
    AF recurrence (primary endpoint) is defined as either failure to recover sinus rhythm in response to direct current cardioversion (DCCV), or relapse of any ECG-confirmed episode of atrial arrhythmia at any time between the DCCV-day and the 8 month follow-up visit.

  2. Co-primary outcome measure: Physical Performance Test (PPT) score (points) [ Time Frame: 8 months ]
    The modified Physical Performance Test (PPT) is derived by evaluating performance in daily activities, with 36 being the best total score for the test. The overall PPT score (co-primary outcome) is derived from performance undertaking six standardized tasks that are timed (walking ~15 m, putting on and removing a coat, picking up a penny ~30 cm in front of the dominant side foot, standing up from a ~40 cm chair, lifting a ~3 kg book to a shelf ~30 cm above shoulder height, climbing one flight of 10 stairs), plus 3 additional tasks (performing a progressive Romberg test with feet side-by-side, semi-tandem and full-tandem, climbing up and down four flights of 10 stairs, and performing a 360-degree turn).


Secondary Outcome Measures :
  1. Atrial fibrillation burden [ Time Frame: 8 months ]
    AF burden by 14-day ECG monitoring (minutes)

  2. Atrial fibrillation symptoms burden (3.25-30) [ Time Frame: 4 & 8 months ]

    Toronto AF Severity Scale (AFSS) score (points) - This is a validated questionnaire encompassing 12-item AF-specific scale, assessing AF symptom burden (range, 3.25 minimally symptomatic episode to 30 highly symptomatic episode) and AF symptom severity (range, 0 no symptoms to 35 severe symptomatology).

    Reference: Dorian P, Jung W, Newman D, et al. The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy. J Am Coll Cardiol 2000;36:1303-9.


  3. Atrial fibrillation symptoms severity (0-35) [ Time Frame: 4 & 8 months ]

    Toronto AF Severity Scale (AFSS) score (points) - This is a validated questionnaire encompassing 12-item AF-specific scale, assessing AF symptom burden (range, 3.25 minimally symptomatic episode to 30 highly symptomatic episode) and AF symptom severity (range, 0 no symptoms to 35 severe symptomatology).

    Reference: Dorian P, Jung W, Newman D, et al. The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy. J Am Coll Cardiol 2000;36:1303-9.


  4. Quality of Life (QoL) [ Time Frame: 4 & 8 months ]
    EuroQoL EQ-5D-5L utility score (points)

  5. Patient Reported Outcome Measures (PROMs) [ Time Frame: 4 & 8 months ]
    Questionnaire (points)

  6. Patient Resource Use Questionnaire (PRUQ) [ Time Frame: 4 & 8 months ]
    Questionnaire (points)

  7. Body mass [ Time Frame: 8 months ]
    Body Weight by weighing scales (kg)

  8. Body composition profile [ Time Frame: 8 months ]
    Total fat (ml) by MRI (Dixon-sequence)

  9. Body composition profile: visceral fat [ Time Frame: 8 months ]
    Visceral fat (ml) by MRI (Dixon-sequence)

  10. Body composition profile: skeletal muscle [ Time Frame: 8 months ]
    Skeletal muscle volumes (ml) by MRI (Dixon-sequence)

  11. Skeletal muscle energetics (quadriceps femoris) [ Time Frame: 8 months ]
    Phosphocreatine (PCr) recovery rate (sec) by 31P magnetic resonance spectroscopy (31P-MRS)

  12. Left ventricular (LV) energetics [ Time Frame: 8 months ]
    LV PCr/ATP ratio by 31P-MRS

  13. Left Ventricular (LV) structure [ Time Frame: 8 months ]
    LV volumes (ml) by cardiac MRI

  14. Left Atrial (LA) structure [ Time Frame: 8 months ]
    LA volumes (ml) by cardiac MRI

  15. Left Ventricular (LV) function [ Time Frame: 8 months ]
    LV function (%) by cardiac MRI

  16. Left Atrial (LA) function [ Time Frame: 8 months ]
    LA function (%) by cardiac MRI

  17. Left Atrial (LA) Flow [ Time Frame: 8 months ]
    LA blood flow (% of stasis) by cardiac MRI

  18. Left Ventricular (LV) Flow [ Time Frame: 8 months ]
    LV blood flow (residual volume %) by cardiac MRI

  19. Epicardial adipose tissue characteristics [ Time Frame: 8 months ]
    Fat attenuation index by CT scan

  20. Health economics outcomes [ Time Frame: through study completion, an average of 2 year ]
    Incremental Cost-Effectiveness Ratio (Cost per Quality-Adjusted Life Year)


Other Outcome Measures:
  1. Skeletal Muscles 1H & 31P Spectroscopy [ Time Frame: 8 months ]
    Assessment of fatty components (IMCL,EMCL), ACC, and mitochondrial function Tau & Qmax

  2. Exploratory analysis of impact of weight loss on epicardial coronary arteries [ Time Frame: 8 months ]
    Fat attenuation index by CT scan



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Persistent AF
  • Body mass index ≥27 kg/m2

Exclusion Criteria:

  • Planned catheter ablation for AF within 8 months
  • Learning difficulties or unable to understand English
  • Participation in another research trial involving an investigational product or weight loss programme in the prior 3 months
  • Current treatment with anti-obesity drugs
  • Contraindication to MR imaging (metal implants or claustrophobia)
  • Uncontrolled endocrine disorders
  • Diabetes requiring insulin
  • Active gout or history of recurrent gout
  • Ongoing gallbladder disease
  • Serious underlying medical or psychiatric disorder; e.g., known cancer or any other significant disease affecting short-term life expectancy; severe valvular disease, myocardial infarction or stroke within the previous 6 months; severe heart failure; eating disorder or purging behaviour; severe psychotic disorder requiring hospitalisation or supervised care, active liver disease (except non-alcoholic fatty liver disease).
  • Unintentional weight loss of more than 5 kg within the prior 6 months
  • Gastrointestinal malabsorption
  • Unstable INR (persistently <2 for >14 days) or supra-therapeutic levels with concomitant bleeding or requiring hospitalisation
  • Substance abuse
  • Taking varenicline (smoking cessation medication)
  • Chronic renal failure of stage 4 or 5
  • Porphyria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03713775


Contacts
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Contact: Marco Spartera, MD +441865234593 marco.spartera@cardiov.ox.ac.uk
Contact: Rohan S Wijesurendra, MBBChirDPhil +441865221867 rohan.wijesurendra@cardiov.ox.ac.uk

Locations
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United Kingdom
Oxford Centre for Magnetic Resonance (OCMR) Recruiting
Oxford, Oxfordshire, United Kingdom, OX3 9DU
Contact: Kathryn Lacey, OM    01865 (2)20 245    kathryn.lacey@cardiov.ox.ac.uk   
Sub-Investigator: Marco Spartera, MD         
Sub-Investigator: Rohan Wijesurendra, MD         
Principal Investigator: Barbara Casadei, MD         
Sponsors and Collaborators
University of Oxford
Investigators
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Principal Investigator: Barbara Casadei, MD DPhil University of Oxford

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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT03713775     History of Changes
Other Study ID Numbers: PID13511-SP001-AC002
242939 ( Other Identifier: IRAS )
First Posted: October 22, 2018    Key Record Dates
Last Update Posted: November 27, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Atrial Fibrillation
Overweight
Weight Loss
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Body Weight
Signs and Symptoms
Body Weight Changes