Modulation of the Intestinal Microbiome by a High Protein Diet (HPD)

• ClinicalTrials.gov Identifier: NCT04812964
• Recruitment Status: Recruiting
• First Posted: March 24, 2021
• Last Update Posted: March 2, 2022
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

Brief Summary:

The objective of this study is to test and determine whether a high protein diet induces weight loss by modulating the composition and function of the intestinal microbiome in obesity. This will be investigated in a randomized clinical study comparing the effect of isocaloric high and normal protein diets on the intestinal microbiome composition, gene content, and metabolome of obese subjects.

Condition or disease	Intervention/treatment	Phase
Obesity	Dietary Supplement: Protein powder supplement, standard dosage based on 0.5 gram protein per pound of subject's lean body mass; Dietary Supplement: Protein powder supplement, High Level Protein, based on 1 gram of protein per pound of lean body mass: 25% protein and 45% carbohydrate	Not Applicable

Detailed Description:

A high protein diet has been shown in preclinical rodent models and clinical trials to be an effective obesity treatment that is associated with greater loss of body weight and fat mass and increased satiety compared to isocaloric standard protein diets. However, the mechanisms of this response have not been fully elucidated. The investigators recently demonstrated in a rodent model that a high protein diet induces shifts in the intestinal microbiome including a bloom of Akkermansia muciniphila, a microbe reported to have an anti-obesity effect. Based on these preliminary studies, the investigators hypothesize that a high protein diet induces alterations in the intestinal microbiome that mediate its clinical efficacy for obesity.

More than three quarters of Veterans are overweight or obese, making obesity a public health problem of tremendous importance to the VA medical system. The results of the proposed study will provide insight into the specific microbes that drive the clinical response to a high protein diet and may identify candidate anti-obesity microbes that could be further developed into novel microbial therapeutics. More broadly, establishing a microbiome-dependent mechanism for the efficacy of a dietary intervention would be a breakthrough in the investigators' understanding of obesity treatment. It would pave the way for larger scale clinical and translational studies investigating the role of the microbiota in other diets and for the development of microbial therapeutics used alone or in combination with dietary intervention to treat obese Veterans.

To investigate the role of the intestinal microbiome in mediating the effect of a high protein diet, the investigators will study 216 overweight and obese Veterans (BMI 27) who will be randomized 1:1 to isocaloric high protein (30%) or normal protein (15%) 1500 calorie diets for 16 weeks utilizing existing clinical infrastructure at the West Los Angeles VA Medical Center established for a recently completed clinical trial of a high protein diet. In Aim 1, the effect of a high protein diet on the composition and function of the intestinal microbiome will be assessed by 16S rRNA sequencing, shotgun metagenomics, and metabolomics. In Aim 2, bioinformatics analysis will be performed to identify fecal microbes, bacterial genes, and metabolites that are associated with weight loss, reduced body fat, decreased hepatic steatosis, altered lipid profiles, reduced hemoglobin A1c, decreased high sensitivity C-reactive protein, increased satiety, and circulating levels of hormones affecting satiety (leptin, ghrelin glucagon, glucagon-like peptide-1, peptide YY).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 216 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Modulation of the Intestinal Microbiome in Obesity by a High Protein Diet
• Actual Study Start Date: April 3, 2018
• Estimated Primary Completion Date: June 30, 2023
• Estimated Study Completion Date: June 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard Diet; Standard protein diet group as control based on 0.5 gram protein per pound of lean body mass with same calories: 15% protein and 55% carbohydrate.	Dietary Supplement: Protein powder supplement, standard dosage based on 0.5 gram protein per pound of subject's lean body mass; Standard protein diet as control, based on 0.5 gram protein per pound of lean body mass, isocaloric (same number of calories) and consisting of 15% protein and 55% carbohydrate.; Other Name: Standard Protein Diet
Active Comparator: High Protein Diet; High protein diet group based on 1 gram of protein per pound of lean body mass: 30% protein and 40% carbohydrate.	Dietary Supplement: Protein powder supplement, High Level Protein, based on 1 gram of protein per pound of lean body mass: 25% protein and 45% carbohydrate; High level of protein diet, based on 1 gram of protein per pound of subject's lean body mass, isocaloric (same number of calories) and consisting of 30% protein and 40% carbohydrate.; Other Name: High Protein Diet

Outcome Measures

Primary Outcome Measures :

1. Weight loss in response to dietary intervention change [ Time Frame: Primary outcome of weight loss is measured at the baseline on Day 1 and at the end of the 16 week study period for each subject. ]
   The primary objective is to compare weight loss between each of the two diets, a high-protein diet versus a standard protein diet.

Secondary Outcome Measures :

1. Change from baseline liver characteristics as measured by fibroscan in response to dietary intervention [ Time Frame: Changes in liver fibrosis and liver steatosis will be measured at baseline and at the end of the 16 week study period for each subject. ]
   Association of change in fat mass and liver steatosis on a high protein diet versus standard protein diet will be measured by fibroscan.
2. Changes in microbiome composition in response to dietary intervention [ Time Frame: Microbiome sampling at 2 weeks will be compared with microbiome composition at the end of the 16 week study period for each subject. ]
   Changes to the intestinal microbiome will be assessed on a high protein diet compared to a standard protein diet.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Men and women between 20 and 60 years of age,
• BMI 27 to 40 kg/m^2,
• non-smoker or stable smoking habits for at least 6 months prior to screening and agreement not to change such habits during the study;
• subjects on non-obesity prescription medication may be included.

Exclusion Criteria:

• Weight change of >3.0 kg in the month prior to screening, weight loss of >10 kg in the 6 months prior to screening,
• calorie restriction diet (<1500 kcal/day) for a period of 4 months or more in the 12 months prior to screening,
• use of any other investigational drug(s) within 8 weeks prior to screening,
• abnormal baseline laboratory parameters (serum creatinine > 1.6 mg/dl; ALT, AST, total bilirubin > 2.0 times the upper limit of normal;
• triglycerides > 500 mg/dl, total cholesterol > 350 mg/dl, TSH outside of normal range),
• consumption of more than 1 alcoholic beverage per day, pregnancy or intention to become pregnant.

Contacts and Locations

Contacts

Contact: Jonathan P Jacobs, MD PhD; (310) 478-3711 ext 48712; Jonathan.Jacobs2@va.gov

Locations

United States, California

VA Greater Los Angeles Healthcare System, West Los Angeles, CA; Recruiting

West Los Angeles, California, United States, 90073

Contact: Jonathan P Jacobs, MD PhD 310-478-3711 ext 48712 Jonathan.Jacobs2@va.gov

Contact: David S Oh, MD (310) 268-3283 David.Oh@va.gov

Principal Investigator: Jonathan P Jacobs, MD PhD

Sponsors and Collaborators

VA Office of Research and Development

Investigators

• Principal Investigator: Jonathan P Jacobs, MD PhD; VA Greater Los Angeles Healthcare System, West Los Angeles, CA

More Information

Publications:

Vu JP, Luong L, Parsons WF, Oh S, Sanford D, Gabalski A, Lighton JR, Pisegna JR, Germano PM. Long-Term Intake of a High-Protein Diet Affects Body Phenotype, Metabolism, and Plasma Hormones in Mice. J Nutr. 2017 Dec;147(12):2243-2251. doi: 10.3945/jn.117.257873. Epub 2017 Oct 25.

Dong TS, Luu K, Lagishetty V, Sedighian F, Woo SL, Dreskin BW, Katzka W, Chang C, Zhou Y, Arias-Jayo N, Yang J, Ahdoot A, Li Z, Pisegna JR, Jacobs JP. A High Protein Calorie Restriction Diet Alters the Gut Microbiome in Obesity. Nutrients. 2020 Oct 21;12(10). pii: E3221. doi: 10.3390/nu12103221.

Stengel A, Goebel-Stengel M, Wang L, Hu E, Karasawa H, Pisegna JR, Taché Y. High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats. Am J Physiol Regul Integr Comp Physiol. 2013 Sep 15;305(6):R582-91. doi: 10.1152/ajpregu.00598.2012. Epub 2013 Jul 24.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT04812964
• Other Study ID Numbers: GAST-030-17S
• First Posted: March 24, 2021
• Last Update Posted: March 2, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:

Obesity; Microbiome; High protein diet

Additional relevant MeSH terms:

Obesity; Overnutrition; Nutrition Disorders; Overweight; Body Weight