Clinical trial NCT02269410: Metabolic Impact of Dietary Protein Supplementation in Surgical Weight Loss
Official title: Metabolic Impact of Dietary Protein Supplementation in Surgical Weight Loss II (MIPS II)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: Bariatric Surgery
Nitrogen Balance
Body composition
Protein supplementation
Satiety
Adherence
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2014-10-21
Enrollment: 6
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The obesity epidemic has grown rapidly in the United States, and is associated with increased morbidity and mortality rates. Bariatric surgery (BS) has emerged as the most effective treatment for severe obesity. Surgical weight loss (WL) is very significant (\~40-50kg) during the first 6-12 months after surgery. The adequate amount of dietary protein during the active period of surgical weight loss is not known. Dietary protein affects body weight regulation: satiety, thermogenesis, energy efficiency and body composition. During diet-induced energy-restriction, sustaining protein intake (PI) at the level of requirement (0.8g /kg ideal body weight (IBW)/ day) appears to preserve fat free mass (FFM) during active WL. PI above requirements (1.2g protein/Kg IBW/ day) results in favorable body composition changes, with greater decrease in fat mass and preservation of FFM, but without effecting WL. Dietary PI 0.8g/day has been associated with greater satiety and increased energy expenditure (EE) during calorie restriction. In this randomized prospective study, the investigators will evaluate the effect of PI on nitrogen balance, body composition, EE and satiety in 40 women undergoing either Gastric Bypass or Vertical Sleeve Gastrectomy, assigned to high protein supplementation (PRO-S), high PRO-S (1.2g /kg IBW/day) or standard- based current guidelines -PRO-S (0.8g /kg IBW/day). PRO-S will be supplied for 3 months after surgery. Outcome measures including nitrogen balance, body composition changes and satiety will be assessed at pre-surgery, and at 3, 6 and 12 months post-surgery. These results will help provide evidence-based data on safe and optimal levels of protein supplementation after BS

Detailed description: The goal of this proposal is to study the effect of dietary protein supplementation (PRO-S) during surgical weight loss, on nitrogen balance, energy expenditure, body composition of weight loss, and satiety. The overall goal is to provide evidence-based data on optimal levels of protein supplementation after surgical weight loss by gastric bypass (GBP), a restrictive and malabsorptive procedure, or by vertical sleeve gastrectomy (VSG), a purely restrictive procedure.

We propose a prospective randomized controlled trial (RCT), in which, patients undergoing either GBP or VSG will be allocated to standard PRO-S recommendation ("standard care" according to the American Society for Metabolic and Bariatric Surgery Guidelines) or high supplementation. We will compare 4 groups of subjects:

* Group 1: GBP Standard PRO-S (0.8g protein/kg ideal body weight (IBW)/day
* Group 2: GBP High PRO-S (1.2g protein/ kg ideal body weight (IBW)/ day)
* Group 3: VSG Standard PRO-S (0.8g protein/kg ideal body weight (IBW)/day
* Group 4: VSG High PRO-S (1.2g protein/ kg ideal body weight (IBW)/ day)

AIM#1: Measure total body nitrogen balance (NB) to assess adequacy of levels of protein intake and protein absorption.

AIM#2: Measure the effect PRO-S on lean body mass (LBM), and resting energy expenditure (REE).

AIM#3: Measure the effect of PRO-S on satiety. Hypothesis 3.1: Patients in the High PRO-S group will experience higher levels of perceived satiety compared with patients in the standard PRO-S group.

AIM #4: Study adherence to protein supplementation. Hypothesis : Adherence will be greater in the Standard PRO-S group.

Background and Significance The obesity epidemic has grown rapidly in the United States, and is associated with increased morbidity and mortality rates. Although preventive measures are needed to solve the obesity epidemic in the long-term, bariatric surgery has become a popular and effective treatment of severe obesity. Obesity and its co-morbidities, including type 2 diabetes (T2DM), have a high health care cost2. The cost is even greater for severe obesity (BMI≥40 kg/m2).

Protein (PRO) malnutrition after bariatric surgery (BS) Bariatric surgery (BS) has emerged as the most effective treatment for severe obesity. Gastric bypass surgery (GBP) results in large weight loss with normalization of metabolic functions, including T2DM remission in \~60-80% of cases. Weight loss is very significant (\~40-50kg). The rate of weight loss is rapid during the first year after surgery. Surgical weight loss can be associated with vitamin, mineral, and protein deficiencies. PRO malnutrition, remains the most severe nutritional complication associated with malabsorptive surgical procedures. The prevalence of protein malnutrition after malabsorptive BS procedures varies between 3 to 18% and is associated with the length of the bypassed segment. The US recommended dietary allowance (RDA) for protein is \~50 g/d for healthy normal weight adults. Experts and clinicians recommend \~70 g/d of protein during low-calorie diets or 60 g/day (standard) and 120 g/day (high) in the earlier months after BS. However, there is little evidence-based data to support these recommendations. In spite of the absence of level 1 data on types and amount of protein recommendations, the American Society for Metabolic Surgery and BS's website has 14 links for commercial nutrition supplements14. In this study, we aim to study protein absorption and adequacy of protein intake by nitrogen balance in patients following standard and high PRO-S following BS.

Effects of dietary proteins Dietary PRO-S and amino acids (AA) are important modulators of body weight by affecting various determinants of body weight regulation: satiety, thermogenesis, energy efficiency and body composition. During energy restriction, sustaining protein intake at the level of requirement (0.8g protein/kg ideal body weight (IBW)/ day) appears to be sufficient to induce body weight loss while preserving fat free mass (FFM). Protein intake above requirements (1.2g protein/Kg IBW/ day) results in a greater decrease in fat mass and preservation of FFM, but has no effect on body weight loss.

Nitrogen balance (NB) study The NB method is classically used to determine adequate protein intakes and to measure whole body protein balance in response to nutritional interventions. Prolonged negative nitrogen balance should not be sustained for long periods due its negative impact on overall health.

Risk of decreased lean body mass (LBM) and resting energy expenditure (REE) with surgical weight loss BS results in large weight losses (30-50kg), with both fat mass (FML) and LBM losses. Our previous observational studies aiming to evaluate the relationship between protein intake and loss of LBM following BS have shown that protein intake \> 60g/ day is associated with better maintenance of LBM after BS. LBM is the main determinant of REE, explaining 75% of the REE variance with REE being the largest component of 24-h energy expenditure (EE). Reduced EE may trigger weight regain in this population. High PRO-S diets may also benefit this population by increasing EE while preventing LBM loss. Increased EE from dietary protein is attributed to an enhanced thermic effect (23-30%) compared to carbohydrates (5-10%) or lipids (2-3%).

Dietary protein intake and satiety High-protein intake increases satiety despite energy restriction. Proposed mechanisms are as follows: a ketogenic state, relatively elevated plasma amino acid (AA) levels, and anorexigenic hormone concentrations feedback on the central nervous system to prolong the duration before one feels hunger for the next meal (satiety) such as, Peptide YY, Glucagon-Like Peptide -1 and cholecystokinin produced in response to peripheral and central detection of amino acid, and decreased levels of the orexigenic hormone ghrelin.

Protein supplementation and adherence Low protein intake after BS has been reported. PRO-S has always been recommended after BS but its feasibility has not been well addressed in any RCT. We will study adherence to PRO-S. Increasing adherence with dietary recommendation is challenging, but may represent a key strategy to improve the clinical nutritional treatment and outcomes after BS.

Eligibility criteria: Inclusion Criteria:

1. Women scheduled to undergo either GBP or VSG.
2. Ethnicity/gender: People of all race/ethnicity are eligible to participate, so that the study will reflect a diverse population.
3. Non diabetic or diet controlled diabetic with no medication

Exclusion Criteria:

1. Individuals who have a clinical history strongly suggestive of type 1 diabetes mellitus or T2DM will be excluded.
2. Nitrogen retention disease such as renal or hepatic disease.
3. Known malabsorption syndrome.
4. Any other condition which, in the opinion of the investigators, may make the candidate unsuitable for participation in this study.

Primary outcomes:
measure: Change in Nitrogen balance (NB)
timeFrame: Change from baseline of NB at 3 months after surgery
measure: Change in Nitrogen balance (NB)
timeFrame: Change form 3 month to 12 months
measure: Change in Nitrogen Balance
timeFrame: Change from baselina to 12 months
Secondary outcomes:
measure: Composite outcome measure consisting of Lean body mass (LBM), and resting energy expenditure (REE).
timeFrame: 0, 3 and 12 months after surgery
measure: Satiety scores
timeFrame: 0, 3 and 12 months
measure: Adherence score to protein supplementation.
timeFrame: 0, 3 and 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Columbia University
name: Blandine Laferrere, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Xavier Pi-Sunyer, MD
role: PRINCIPAL_INVESTIGATOR
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