The Effects of a High Protein Diet on Microbiota, Gastrointestinal Function and Wellness in Older Women

Study Overview
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Brief Summary
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The purpose of the proposed study is to determine the effects of consuming a high protein diet on fecal microbial communities, gastrointestinal function and symptoms, and general wellness in older adults.

Detailed Description
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Older women will be randomized to a 18-week crossover study design. During each treatment period participants will be provided with a weight maintenance diet providing approximately 2 g/kg/day of protein. Following a two-week baseline and in random order will have the following diets assigned: The participants will be provided with a weight maintenance, high protein diet for two weeks, then for two-weeks will resume their normal diet; The participants will come back into clinic and for the next two weeks to receive a high protein diet with a multi-strain probiotic for two weeks, then for two-weeks will resume their normal diet; The participants will come back into clinic and for the next two weeks will receive a high protein diet with a prebiotic, then for two-weeks will resume their normal diet; The participants will come back into clinic and for the next two weeks will receive a high protein diet with the synbiotic combination. then for two-weeks will resume their normal diet Participants and researchers will be blinded for each treatment period (participants will receive a probiotic or placebo capsule, and a prebiotic or placebo sachet). The following will be performed during the clinic visits: Questionnaires will assess quality of life (QoL), wellness, gastrointestinal symptoms, bowel movement frequency, and compliance. Hand-grip strength will be measured. Blood and urine samples will be collected at baseline and at weeks 2, 6,10 and 14. Stool samples will be collected at baseline and at weeks 2, 4, 6, 8,10, 12, 14 and 16.

Official Title
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The Effects of a High Protein Diet on Microbiota, Gastrointestinal Function, Wellness and the Potential Mitigating Effects of a Multi-strain Probiotic, Prebiotic, and Synbiotic: a Randomized, Double-blinded Crossover Study in Older Women.

Conditions
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Aging

Intervention / Treatment
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* Dietary Supplement: Probiotic capsule and Fiber Sachet
* Dietary Supplement: Probiotic capsule and Placebo sachet
* Dietary Supplement: Placebo capsule and Fiber Sachet
* Dietary Supplement: Placebo capsule and Placebo sachet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To participate in the study you must be a woman 65 years of age or older be willing to complete daily and weekly questionnaires be willing to wear a SenseWear Pro Armband (BodyMedia, Inc.) to monitor energy expenditure and establish dietary energy needs be willing to provide blood samples, stool samples, and urine samples throughout the course of the study be willing to discontinue prebiotics, probiotics and/or any fiber supplements for the duration of the study be willing to consume the provided diet for the designated 8 weeks of the study are willing to report and maintain their usual alcohol intake throughout the study are able to take foods, study fiber, probiotic, and placebo without the aid of another person able to attend all scheduled study appointments for the duration of the study have a usual protein intake consistent with United States' population as assessed by dietary analysis have a usual fiber intake consistent with United States' population as assessed by dietary analysis be willing to provide a social security number to receive study payment. Exclusion Criteria: To participate in the study you must NOT have a physician-diagnosed gastrointestinal disease or condition (such as ulcerative colitis, Crohn's disease, gastroparesis, peptic ulcer disease, cancer, celiac disease, short bowel disease, ileostomy) have had or are currently being treated for any known illnesses or conditions that may impact perceived health such as HIV/AIDS, immune modulating diseases (autoimmune, hepatitis, cancer, etc.), diabetes or chronic kidney disease be a vegetarian have any known food allergies or dietary restrictions be currently taking medication for constipation or diarrhea have taken antibiotics within the past 2 months be a current smoker be planning on loosing/gaining weight during the next 6 months typically consume no more than one alcoholic beverage per day have a BMI greater than 30

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic capsule and Fiber sachet<br>Participants will be randomly assigned to receive all of the following in random order: a probiotic capsule and fiber sachet daily for 2-weeks, a probiotic capsule and placebo sachet for 2-weeks, a fiber sachet and placebo capsule for 2-weeks, and placebo capsule and placebo sachet for 2-weeks. Each treatment period is separated by a 2-week washout. During each treatment period, in addition to consuming a probiotic capsule or placebo and/or a fiber sachet or placebo sachet participants will be on a controlled higher protein diet. | Dietary Supplement: Probiotic capsule and Placebo sachet<br>* A probiotic capsule and placebo sachet will be consumed daily for 2-weeks. The probiotic capsule contains a mixture of Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus acidophilus and Lactobacillus plantarum. The placebo sachet consists of 5 g of maltodextrin. During the treatment period, in addition to consuming the probiotic capsule and placebo sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>Dietary Supplement: Placebo capsule and Fiber Sachet<br>* A placebo capsule and fiber sachet will be consumed daily for 2-weeks. The placebo capsule will contain potato starch, magnesium stearate and ascorbic acid. The fiber sachet consists of 5 g of chicory root fiber. During the treatment period, in addition to consuming the placebo capsule and fiber sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>Dietary Supplement: Placebo capsule and Placebo sachet<br>* A placebo capsule and placebo sachet will be consumed daily for 2-weeks. The placebo capsule will contain potato starch, magnesium stearate and ascorbic acid. The fiber sachet consists of 5 g of maltodextrin. During the treatment period, in addition to consuming the placebo capsule and placebo sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>|
| Experimental: Probiotic capsule and Placebo sachet<br>Participants will be randomly assigned to receive all of the following in random order: a probiotic capsule and fiber sachet daily for 2-weeks, a probiotic capsule and placebo sachet for 2-weeks, a fiber sachet and placebo capsule for 2-weeks, and placebo capsule and placebo sachet for 2-weeks. Each treatment period is separated by a 2-week washout. During each treatment period, in addition to consuming a probiotic capsule or placebo and/or a fiber sachet or placebo sachet participants will be on a controlled higher protein diet. | Dietary Supplement: Probiotic capsule and Fiber Sachet<br>* A probiotic capsule and fiber sachet will be consumed daily for 2-weeks. The probiotic capsule contains a mixture of Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus acidophilus and Lactobacillus plantarum. The fiber sachet consists of 5 g of chicory root fiber. During the treatment period, in addition to consuming the probiotic capsule and fiber sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>Dietary Supplement: Placebo capsule and Fiber Sachet<br>* A placebo capsule and fiber sachet will be consumed daily for 2-weeks. The placebo capsule will contain potato starch, magnesium stearate and ascorbic acid. The fiber sachet consists of 5 g of chicory root fiber. During the treatment period, in addition to consuming the placebo capsule and fiber sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>Dietary Supplement: Placebo capsule and Placebo sachet<br>* A placebo capsule and placebo sachet will be consumed daily for 2-weeks. The placebo capsule will contain potato starch, magnesium stearate and ascorbic acid. The fiber sachet consists of 5 g of maltodextrin. During the treatment period, in addition to consuming the placebo capsule and placebo sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>|
| Experimental: Placebo capsule and Fiber sachet<br>Participants will be randomly assigned to receive all of the following in random order: a probiotic capsule and fiber sachet daily for 2-weeks, a probiotic capsule and placebo sachet for 2-weeks, a fiber sachet and placebo capsule for 2-weeks, and placebo capsule and placebo sachet for 2-weeks. Each treatment period is separated by a 2-week washout. During each treatment period, in addition to consuming a probiotic capsule or placebo and/or a fiber sachet or placebo sachet participants will be on a controlled higher protein diet. | Dietary Supplement: Probiotic capsule and Fiber Sachet<br>* A probiotic capsule and fiber sachet will be consumed daily for 2-weeks. The probiotic capsule contains a mixture of Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus acidophilus and Lactobacillus plantarum. The fiber sachet consists of 5 g of chicory root fiber. During the treatment period, in addition to consuming the probiotic capsule and fiber sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>Dietary Supplement: Probiotic capsule and Placebo sachet<br>* A probiotic capsule and placebo sachet will be consumed daily for 2-weeks. The probiotic capsule contains a mixture of Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus acidophilus and Lactobacillus plantarum. The placebo sachet consists of 5 g of maltodextrin. During the treatment period, in addition to consuming the probiotic capsule and placebo sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>Dietary Supplement: Placebo capsule and Placebo sachet<br>* A placebo capsule and placebo sachet will be consumed daily for 2-weeks. The placebo capsule will contain potato starch, magnesium stearate and ascorbic acid. The fiber sachet consists of 5 g of maltodextrin. During the treatment period, in addition to consuming the placebo capsule and placebo sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>|
| Placebo Comparator: Placebo capsule and Placebo sachet<br>Participants will be randomly assigned to receive all of the following in random order: a probiotic capsule and fiber sachet daily for 2-weeks, a probiotic capsule and placebo sachet for 2-weeks, a fiber sachet and placebo capsule for 2-weeks, and placebo capsule and placebo sachet for 2-weeks. Each treatment period is separated by a 2-week washout. During each treatment period, in addition to consuming a probiotic capsule or placebo and/or a fiber sachet or placebo sachet participants will be on a controlled higher protein diet. | Dietary Supplement: Probiotic capsule and Fiber Sachet<br>* A probiotic capsule and fiber sachet will be consumed daily for 2-weeks. The probiotic capsule contains a mixture of Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus acidophilus and Lactobacillus plantarum. The fiber sachet consists of 5 g of chicory root fiber. During the treatment period, in addition to consuming the probiotic capsule and fiber sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>Dietary Supplement: Probiotic capsule and Placebo sachet<br>* A probiotic capsule and placebo sachet will be consumed daily for 2-weeks. The probiotic capsule contains a mixture of Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus acidophilus and Lactobacillus plantarum. The placebo sachet consists of 5 g of maltodextrin. During the treatment period, in addition to consuming the probiotic capsule and placebo sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>Dietary Supplement: Placebo capsule and Fiber Sachet<br>* A placebo capsule and fiber sachet will be consumed daily for 2-weeks. The placebo capsule will contain potato starch, magnesium stearate and ascorbic acid. The fiber sachet consists of 5 g of chicory root fiber. During the treatment period, in addition to consuming the placebo capsule and fiber sachet participants will consume a controlled diet consisting of foods that provide an average of approximately 2 g/kg/day of protein.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiota Studies (recovery) | Change in the concentrations of the probiotic strains in the stools will be measured with strain specific deoxyribonucleic acid (DNA) (or antibodies) in fecal samples (e.g. quantitative polymerase chain reaction (qPCR), flow cytometry). | Change from Baseline at Week 2,4,6,8,10,12,14,16 | 
| Microbiota Studies (overall composition) | Effects of the probiotic interventions on overall microbiota composition (e.g. 454 16S rRNA (ribosomal ribonucleic acid) sequencing) will also be measured. | Change from Baseline at Week 2,4,6,8,10,12,14,16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Digestive Health (Gastrointestinal Symptom Rating Scale ) | Measured by gastrointestinal symptoms (gas, bloating, diarrhea, etc.) assessed using the weekly Gastrointestinal Symptom Rating Scale (GSRS). | Change from Baseline at Week 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18 | 
| Digestive Health (Bristol Stool Scale) | Measured by gastrointestinal symptoms (gas, bloating, diarrhea, etc.) assessed using a daily questionnaire. The daily questionnaire will include questions regarding symptoms and the Bristol Stool Scale (stool form and transit). | Change from Baseline at Week 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18 | 
| Blood Analysis (metabolic) | Measured by comprehensive Metabolic Panel | Change from Baseline at Weeks 2,6,10,14 | 
| Blood Analysis (lipids) | Measured by Lipid Panel | Change from Baseline at Weeks 2,6,10,14 | 
| Blood Analysis (inflammation) | Measured by Inflammatory markers | Change from Baseline at Weeks 2,6,10,14 | 
| Blood Analysis (blood count) | Measured by Complete Blood Count (CBC) | Change from Baseline at Weeks 2,6,10,14 | 
| Blood Analysis (signalling) | Measured by (mammalian target of rapamycin) mTOR | Change from Baseline at Weeks 2,6,10,14 | 
| Blood Analysis (regulation) | Measured by insulin-like growth factor 1 (IGF-1) | Change from Baseline at Weeks 2,6,10,14 | 
| Blood Analysis (proteolysis) | Measured by total p-cresol | Change from Baseline at Weeks 2,6,10,14 | 
| General Wellness | Individual reporting of antibiotic usage, visits to a physician, etc. | Day 1 through 126 | 
| Proteolytic Activity | Measured by urinary p-cresol, indoxyl sulfate and urine urea nitrogen (UUN) | Change from Baseline at Weeks 2,6,10,14 | 
| Measures of Quality of Life (QoL) | QoL questionnaire (domains such as physical functioning, general health, bodily pain, vitality, social functioning), questionnaire to assess frailty, and hand grip strength | Change from Baseline at Weeks 2,6,10,14 | 
| Measures of Well-being (frailty) | Questionnaire to assess frailty | Change from Baseline at Weeks 2,6,10,14 | 
| Measures of Well-being (hand grip) | Hand grip strength will be measured | Change from Baseline at Weeks 2,6,10,14 | 
| Acceptability of the Diet | Acceptability will be measured using the daily questionnaire and participant compliance recordings/logs of any unconsumed foods during treatment periods | Day 1 through 126 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotics, prebiotics, high protein diet, microbiota