Sub-Study of the PREVIEW Study Australia

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by University of Sydney
Sponsor:
Information provided by (Responsible Party):
University of Sydney
ClinicalTrials.gov Identifier:
NCT02030249
First received: December 12, 2013
Last updated: January 7, 2014
Last verified: January 2014
  Purpose

The aim of this study is to investigate possible enduring effects of a standard 2-month weight loss program on appetite regulation, bone homeostasis and muscle strength in younger and older adults, as well as the impact of differences in dietary composition during weight maintenance.


Condition Intervention
Pre-diabetes
Obesity
Behavioral: Low calorie diet administered from 0 to 2 months
Behavioral: High Protein / Low Glycaemic Index
Behavioral: Moderate Protein / High Glycaemic Index

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sub-Study of the PREVIEW Study Australia: Effects of Weight Loss on Appetite, Bone Mass and Muscle Strength

Resource links provided by NLM:


Further study details as provided by University of Sydney:

Primary Outcome Measures:
  • Fasting appetite [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Previous research has shown that 2 months on a weight reducing diet increases appetite in the fasting state. There is some suggestion that this diet-induced increase in appetite is sustained even after following a weight maintenance diet for 12 months. The investigators will assess fasting appetite, as measured using visual analogue scales, at 0, 2, 6 and 12 months after commencement of the 2-month standardized weight loss diet. The 6- and 12-month time points are taken after 4 and 10 months on the different weight maintenance programs. This primary outcome (fasting appetite at 12 months) will demonstrate whether the weight-loss-induced increase in fasting appetite that is anticipated at 2 months will be normalized by the 12 month time point, and whether the type of weight maintenance diet (High Protein / Low Glycaemic Index versus Moderate Protein / High Glycaemic Index) influences this.

  • Fasting plasma concentrations of gut-derived appetite-regulating hormones [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Previous research has shown that 2 months on a weight reducing diet alters fasting plasma concentrations of gut-derived appetite regulating hormones in a way that would be expected to increase appetite (i.e. increased ghrelin and decreased peptide YY). There is some suggestion that this change in gut hormone concentrations is sustained even after following a weight maintenance diet for 12 months. The investigators will assess fasting plasma concentrations of gut-derived appetite-regulating hormones (ghrelin and peptide YY) at 0, 2, 6 and 12 months after commencement of the 2-month standardized weight loss diet. The 6- and 12-month time points are taken after 4 and 10 months on the 2 different weight maintenance programs. This primary outcome will demonstrate whether the weight-loss-induced increases in ghrelin and decrease in peptide YY that are anticipated at 2 months will be normalized by the 12 month time point, and whether the type of weight maintenance diet influences this.

  • Bone mass [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    The investigators will assess bone mineral density and bone mineral content in the lumbar spine and hip (or wrist for people in whom arthritis interferes with the reading) via dual energy X-ray absorptiometry (DXA) immediately before and after the 2-month standardized weight loss program (i.e. at 0 and 2 months). This primary outcome will help determine whether there is a difference between younger and older participants with respect to changes in bone mass with weight reduction.

  • Bone turnover [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    The investigators will assess serum concentrations of bone turnover markers immediately before and after the 2-month standardized weight loss program (i.e. at 0 and 2 months). The bone turnover markers to be measured are serum procollagen type-I N-propeptide (P1NP, a marker of bone formation) and serum C-telopeptide of type-I collagen (CTX, a marker of bone resorption). This primary outcome will show whether there is a difference between younger and older participants with respect to changes in bone turnover with weight reduction. This primary outcome is important because DXA scanning to assess bone mass can result in artefactual results in people who are are obese or undergoing changes in body fat mass, as will be the case in this trial.


Secondary Outcome Measures:
  • Fasting appetite [ Time Frame: 0 months ] [ Designated as safety issue: No ]
    Please see description for fasting appetite at 12 months (primary outcome measure).

  • Fasting appetite [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Please see description for fasting appetite at 12 months (primary outcome measure).

  • Fasting appetite [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Please see description for fasting appetite at 12 months (primary outcome measure).

  • Fasting plasma concentrations of gut-derived appetite-regulating hormones [ Time Frame: 0 months ] [ Designated as safety issue: No ]
    Please see description for fasting plasma concentrations of gut-derived appetite-regulating hormones at 12 months (primary outcome measure).

  • Fasting plasma concentrations of gut-derived appetite-regulating hormones [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Please see description for fasting plasma concentrations of gut-derived appetite-regulating hormones at 12 months (primary outcome measure).

  • Fasting plasma concentrations of gut-derived appetite-regulating hormones [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Please see description for fasting plasma concentrations of gut-derived appetite-regulating hormones at 12 months (primary outcome measure).

  • Bone mass [ Time Frame: 0 months ] [ Designated as safety issue: No ]
    Please see description for bone mass at 2 months (primary outcome measure).

  • Bone mass [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    If the investigators see a change from baseline in bone mass (bone mineral density or bone mineral content) or bone turnover (serum P1NP or CTX concentrations) after the 2-month low calorie diet in the younger or older participants, then they will measure bone mass again at 6 months, to determine whether any such change from baseline is maintained after 4 months on the two different weight maintenance programs. This secondary outcome will enable determination of whether any effects of the 2-month low calorie diet on bone mass are sustained at 6 months, and whether the type of weight maintenance diet (High Protein / Low Glycaemic Index versus Moderate Protein / High Glycaemic Index) influences this.

  • Bone mass [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Please see description for bone mass at 6 months.

  • Bone mass [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Please see description for bone mass at 6 months.

  • Bone mass [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Please see description for bone mass at 6 months.

  • Bone turnover [ Time Frame: 0 months ] [ Designated as safety issue: No ]
    Please see description for bone turnover at 2 months (primary outcome measure).

  • Bone turnover [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    If the investigators see a change from baseline in bone mass (bone mineral density or bone mineral content) or bone turnover (serum P1NP or CTX concentrations) after the 2-month low calorie diet in the younger or older participants, then they will measure bone turnover again at 6 months, to determine whether any such change from baseline is maintained after 4 months on the two different weight maintenance programs. This secondary outcome will enable determination of whether any effects of the 2-month low calorie diet on bone turnover are sustained at 6 months, and whether the type of weight maintenance diet (High Protein / Low Glycaemic Index versus Moderate Protein / High Glycaemic Index) influences this.

  • Bone turnover [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Please see description for bone turnover at 6 months.

  • Bone turnover [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Please see description for bone turnover at 6 months.

  • Bone turnover [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Please see description for bone turnover at 6 months.

  • Modulators of bone turnover [ Time Frame: 0 months ] [ Designated as safety issue: No ]
    If there is a change in bone mass (bone mineral density or bone mineral content), or a change in bone turnover (serum P1NP or serum CTX) with the 2-month standardized weight loss program, then the investigators will measure the following modulators of bone turnover, pending funding availability: serum 25-OH vitamin D, serum parathyroid hormone, serum calcium, serum phosphate, serum albumin and serum creatine. This outcome measure will help to elucidate possible mechanisms for any observed changes in bone mass or bone turnover.

  • Modulators of bone turnover [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Please see description for modulators of bone turnover at 0 months.

  • Modulators of bone turnover [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Please see description for modulators of bone turnover at 0 months.

  • Modulators of bone turnover [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Please see description for modulators of bone turnover at 0 months.

  • Modulators of bone turnover [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Please see description for modulators of bone turnover at 0 months.

  • Modulators of bone turnover [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Please see description for modulators of bone turnover at 0 months.

  • Muscle (handgrip) strength [ Time Frame: 0 months ] [ Designated as safety issue: No ]
    Muscle (handgrip) strength will be determined with a handheld dynamometer. This secondary outcome measure aims to determine whether the standardized 2-month weight loss diet induces changes in muscle strength, and whether there is any differential effect in younger versus older participants.

  • Muscle (handgrip) strength [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Please see description for muscle (handgrip) strength at 0 months.

  • Muscle (handgrip) strength [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    If the investigators see a change from baseline in muscle (handgrip) strength after the 2-month low calorie diet in the younger or older participants, then they will measure muscle (handgrip) strength again at 6 months, to determine whether any such change from baseline is maintained after 4 months on the two different weight maintenance programs. This secondary outcome will enable determination of whether any effects of the 2-month low calorie diet on muscle (handgrip) strength are sustained at 6 months, and whether the type of weight maintenance diet (High Protein / Low Glycaemic Index versus Moderate Protein / High Glycaemic Index) influences this.

  • Muscle (handgrip) strength [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Please see description for muscle (handgrip) strength at 6 months.

  • Muscle (handgrip) strength [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Please see description for muscle (handgrip) strength at 6 months.

  • Muscle (handgrip) strength [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Please see description for muscle (handgrip) strength at 6 months.


Other Outcome Measures:
  • Urinary N-terminal telopeptide [ Time Frame: 0 months ] [ Designated as safety issue: No ]
    Urinary N-terminal telopeptide (NTX) is a marker of bone resorption. While the investigators have selected to measure serum CTX as their marker of bone turnover (resorption), some laboratories in Australia and around the world still use NTX as a marker of bone resorption. The investigators will thus collect urine samples for the potential assay of NTX, should a journal reviewer request this data upon review of our resultant manuscript, and provided that funding is available.

  • Urinary N-terminal telopeptide [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    Please see description for urinary N-terminal telopeptide at 0 months.

  • Urinary N-terminal telopeptide [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Please see description for urinary N-terminal telopeptide at 0 months.

  • Urinary N-terminal telopeptide [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Please see description for urinary N-terminal telopeptide at 0 months.

  • Urinary N-terminal telopeptide [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Please see description for urinary N-terminal telopeptide at 0 months.

  • Urinary N-terminal telopeptide [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Please see description for urinary N-terminal telopeptide at 0 months.


Estimated Enrollment: 292
Study Start Date: January 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High Protein / Low Glycaemic Index
A 10-month weight maintenance diet, administered from the 2-month to the 12-month time point, where protein intake is 25% of energy intake, carbohydrate intake is 45% of energy intake, dietary glycaemic index is < 55. Please see parent study for further Arm details: http://clinicaltrials.gov/ct2/show/NCT01777893?term=preview&rank=1
Behavioral: Low calorie diet administered from 0 to 2 months
The 2-month low calorie diet is administered from the 0 months to the 2 months time point. It is designed to elicit a weight loss of 8% of initial body weight. Please see parent study for further intervention details: http://clinicaltrials.gov/ct2/show/NCT01777893?term=preview&rank=1
Other Names:
  • 2-month low calorie diet
  • 2-month standardized low calorie diet
  • 2-month Cambridge Diet
  • 2-month low energy diet
Behavioral: High Protein / Low Glycaemic Index
Please see description of the Arm by the same name.
Active Comparator: Moderate Protein / High Glycaemic Index
A 10-month weight maintenance diet, administered from the 2-month to the 12-month time point, where protein intake is 15% of energy intake, carbohydrate intake is 55% of energy intake, dietary glycaemic index is > 65. Please see parent study for further Arm details: http://clinicaltrials.gov/ct2/show/NCT01777893?term=preview&rank=1
Behavioral: Low calorie diet administered from 0 to 2 months
The 2-month low calorie diet is administered from the 0 months to the 2 months time point. It is designed to elicit a weight loss of 8% of initial body weight. Please see parent study for further intervention details: http://clinicaltrials.gov/ct2/show/NCT01777893?term=preview&rank=1
Other Names:
  • 2-month low calorie diet
  • 2-month standardized low calorie diet
  • 2-month Cambridge Diet
  • 2-month low energy diet
Behavioral: Moderate Protein / High Glycaemic Index
Please see description of the Arm by the same name.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   25 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 25 - 45 years and 55 - 70 years
  • Overweight or obesity status BMI>25 kg/m2
  • Pre-diabetes. The criteria from WHO/IDF (International Diabetes Foundation) for assessing pre-diabetes will be used as the formal inclusion criteria, i.e. having: Impaired Fasting Glucose (IFG): Fasting venous plasma glucose concentration 5.6 - 6.9 mmol/l or Impaired Glucose Tolerance (IGT): Venous Plasma glucose concentration of 7.8 - 11.0 mmol/l at 2 h after oral administration of 75 g glucose (oral glucose tolerance test, OGTT), with fasting plasma glucose less than 7.0 mmol/l. Due to potential between-lab variation (local assessments), HbA1c is not used as an inclusion criteria in the screening.
  • Informed consent required
  • Ethnic group - No restrictions
  • Smoking - Smoking is allowed, provided subjects have not recently (within 1 month) changed habits. However, smoking status is monitored throughout the study and used as a confounding variable.
  • Motivation - Motivation and willingness to be randomized to any of the groups and to do his/hers best to follow the given protocol
  • Other - Able to participate at CID's during normal working hours.

Exclusion Criteria:

Based on interview and/or questionnaire, individuals with the following problems will be excluded:

  • Medical conditions as known by the subjects: Diabetes mellitus (other than gestational diabetes mellitus); Significant cardiovascular disease including current angina; myocardial infarction or stroke within the past 6 months; heart failure; symptomatic peripheral vascular disease; Systolic blood pressure above 160 mmHg and/or diastolic blood pressure above 100 mmHg whether on or off treatment for hypertension. If being treated, no change in drug treatment within last 3 months; Advanced chronic renal impairment; Significant liver disease e.g. cirrhosis (fatty liver disease allowed); Malignancy which is currently active or in remission for less than five years after last treatment (local basal and squamous cell skin cancer allowed); Active inflammatory bowel disease, celiac disease, chronic pancreatitis or other disorder potentially causing malabsorption; Previous bariatric surgery; Chronic respiratory, neurological, musculoskeletal or other disorders where, in the judgement of the investigator, participants would have unacceptable risk or difficulty in complying with the protocol (e.g. physical activity program); A recent surgical procedure until after full convalescence (investigators judgement); Transmissible blood-borne diseases e.g. hepatitis B, HIV; Psychiatric illness (e.g. major depression, bipolar disorder).
  • Medication: Use currently or within the previous 3 months of prescription medication that has the potential of affecting body weight or glucose metabolism such as glucocorticoids (but excluding inhaled and topical steroids; bronchodilators are allowed), psychoactive medication, epileptic medication, or weight loss medications (either prescription, over the counter or herbal). Low dose antidepressants are allowed if they, in the judgement of the investigator, do not affect weight or participation to the study protocol. Levothyroxine for treatment of hypothyroidism is allowed if the participant has been on a stable dose for at least 3 months.
  • Personal/Other: Engagement in competitive sports; Self-reported weight change of >5 % (increase or decrease) within 2 months prior to screening; Special diets (e.g. vegan, Atkins) within 2 months prior to study start. A lacto-vegetarian diet is allowed; Severe food intolerance expected to interfere with the study; Regularly drinking > 21 alcoholic units/week (men), or > 14 alcoholic units/week (women); Use of drugs of abuse within the previous 12 months; Blood donation or transfusion within the past 1 month before baseline or CID's; Self-reported eating disorders; Pregnancy or lactation, including plans to become pregnant within the next 36 months; No access to either phone or Internet (this is necessary when being contacted by the instructor's during the maintenance phase); Adequate understanding of national language; Psychological or behavioral problems which, in the judgement of the investigator, would lead to difficulty in complying with the protocol.
  • Laboratory screening: If all of the above criteria are satisfied, the participant is eligible for a glucose tolerance test (blood at 0 and 120 mins), and blood glucose concentrations are analyzed immediately (Haemocue). In addition full blood count, urea, and electrolytes may be analyzed as a further safety evaluation.
  • ONLY IF the glucose tolerance test meets the entry criteria for the study, the remaining samples are sent to the local laboratory for a safety check, with the following exclusion criteria: Hemoglobin concentration below local laboratory reference values (i.e. anemia); Creatinine >1.5 times Upper Limit of Normal (local laboratory reference values); Alanine Transaminase (ALT) and/or Aspartate Transaminase (AST) >3 times the Upper Limit of Normal (local laboratory reference values); Or any other significant abnormality on these tests which in the investigators opinion may be clinically significant and require further assessment.
  • Electrocardiography (ECG). Any abnormality which in the opinion of the investigator might indicate undiagnosed cardiac disease requiring further assessment (e.g. significant conduction disorder, arrhythmia, pathological Q waves). This is done in adults 55-70 years of age.
  • After LCD phase (in adults): Failure to reach at least 8% weight reduction during the LCD phase. This leads to exclusion from the intervention.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02030249

Contacts
Contact: Amanda Salis (nee Sainsbury), PhD + 61 (0) 423 777 801 ext - amanda.salis@sydney.edu.au
Contact: Roslyn Muirhead, PhD +61 2 9036 3024 ext - roslyn.muirhead@sydney.edu.au

Locations
Australia, New South Wales
The University of Sydney Not yet recruiting
Camperdown, New South Wales, Australia, 2006
Contact: Amanda Salis (nee Sainsbury), PhD    + 61 (0) 423 777 801    amanda.salis@sydney.edu.au   
Contact: Roslyn Muirhead, PhD    +61 2 9036 3024    roslyn.muirhead@sydney.edu.au   
Principal Investigator: Amanda Salis (nee Sainsbury), PhD         
Principal Investigator: Jennie Brand-Miller, PhD         
Principal Investigator: Stephen Coliaguri, MBBS PhD         
Principal Investigator: Stephen Simpson, PhD         
Principal Investigator: Ian D Caterson, MBBS PhD         
Principal Investigator: Anthony Keech, MBBS PhD         
Principal Investigator: Tania Markovic, MBBS PhD         
Sub-Investigator: Annie Simpson, BSc         
Sub-Investigator: Roslyn Muirhead, PhD         
Sub-Investigator: Meredith Porter, BSc         
Sub-Investigator: Shannon Overs, BSc         
Sub-Investigator: Radhika Seimon, PhD         
Sub-Investigator: Lauren N Franks         
Sub-Investigator: Jessica-Isabell Zibellini         
Sub-Investigator: Arpita Das, BSc         
Garvan Institute of Medical Research Not yet recruiting
Darlinghurst, Sydney, New South Wales, Australia, 2010
Contact: Jacqueline Center, MBBS PhD       j.center@garvan.org.au   
Principal Investigator: Jacqueline Center, MBBS PhD         
Prince of Wales Hospital Not yet recruiting
Randwick, Sydney, New South Wales, Australia, 2031
Contact: Chris White, MBBS PhD    + 61 2 9382 4813    Chris.White@SESIAHS.HEALTH.NSW.GOV.AU   
Principal Investigator: Chris White, MBBS PhD         
Sponsors and Collaborators
University of Sydney
Investigators
Principal Investigator: Amanda Salis (nee Sainsbury), PhD The University of Sydney
  More Information

Additional Information:
Publications:

Responsible Party: University of Sydney
ClinicalTrials.gov Identifier: NCT02030249     History of Changes
Other Study ID Numbers: 2013/535 - SUB-STUDY, KBBE-CALL- 6-Nr. 312057
Study First Received: December 12, 2013
Last Updated: January 7, 2014
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by University of Sydney:
Low calorie diet
Diet - reducing
Pre-diabetes
Obesity
Appetite
Visual analogue scale
Ghrelin
Peptide YY
Bone mass
Bone turnover
Muscle strength

Additional relevant MeSH terms:
Diabetes Mellitus
Obesity
Glucose Intolerance
Prediabetic State
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperglycemia

ClinicalTrials.gov processed this record on July 23, 2014