Effects of Oral Microbial Protease Supplementation on Postprandial Plasma Amino Acid Concentrations and Appetite in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Early (0-2 h) postprandial plasma total amino acid concentration incremental area-under-the-curve (P3 - WHEY vs. placebo treatment)
研究概览
简要总结
The primary purpose of this study is to assess the effect of co-ingestion of microbial proteases and whey protein concentrate (WPC) on postprandial plasma amino acid concentrations in healthy adult participants compared to WPC with placebo. The secondary purpose is to assess the effect of co-ingestion of microbial proteases and WPC on postprandial glycemic response, subjective appetite sensations, gut-derived appetite regulating hormones, ad libitum meal intake, and gastrointestinal tolerability in healthy adult participants compared to WPC with placebo.
详细描述
A within-subject crossover design will be used for this randomized, double-blind, placebo-controlled study in health adults to assess the efficacy of a microbial protease mixture (from Aspergillus species) on enhancing postprandial aminoacidemia after consumption of a whey protein shake. There are two treatment groups in this crossover trial, including one microbial protease group and one placebo group. A total of 24 participants will be enrolled and undergo both treatment phases with a minimum 7-day washout.
The study will last no less than 8 days and up to 72 days for each participant, including screening, washout, and end of study (EOS) visit. The study will include a screening visit (Visit 1) followed by a screening period lasting up to 30 days, the phase 1 aminoacidemia trial on Day 1 (Visit 2), minimum 7-day washout with a window of +35 days, followed by the phase 2 aminoacidemia trial (EOS Visit 3, Day 8 +35 days).
During the aminoacidemia trials, participants will arrive to the clinic in a fasted state, and 31.9 grams whey protein concentrate (WPC) in 300 mL water with microbial proteases or placebo will be administered. Blood will be collected at baseline and 11 postprandial timepoints across 4 hours for plasma amino acid, glucose, and insulin quantitation. Blood will also be utilized for quantitation of the anorexigenic, satiety-related peptide hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), and the orexigenic peptide hormone ghrelin.
Additionally, changes in appetite sensations will be assessed by visual analog score (VAS) responses to 5 questions at baseline, directly after consumption of study products, and postprandially every half hour. Palatability of the study products will be assessed by 5-item Palatability Questionnaire. Gastrointestinal tolerability will be assessed by 8-item modified Gastrointestinal Tolerance Questionnaire (mGITQ) at the end of the 4-hour aminoacidemia trial.
To further investigate appetite and satiety, an test meal will be provided at 4 hours for the determination of energy intake, followed by a final appetite VAS questionnaire immediately after the test meal. The maximum time to finish the test meal is 30 minutes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult female or male participants who are 20 to 40 years of age at screening (inclusive)
- •Has a BMI between 18.5 to 29.9 kg·m^(-2) (inclusive) at Visit 1
- •In good general health (no uncontrolled diseases or conditions) as deemed by the investigator and able to consume the study product
- •Individuals with childbearing potential must agree to practice an acceptable form of birth control (i.e., use for at least 3 months prior to the first dose of study product: hormonal contraceptives including oral contraceptives, hormone birth control patch (e.g., Ortho Evra), or hormone implant (e.g., Norplant System); or condoms)
- •Has maintained stable use of medication and supplements defined in the study protocol (Section 7.6), stable dietary and lifestyle habits, and stable body weight, for the last 3 months prior to screening and agree to maintain them throughout the study
- •Agree to avoid strenuous exercise 48 hours prior to each visit
- •Willing to limit daily alcohol consumption to no more than 3 standard drinks per day throughout the study, and agree to entirely avoid alcohol consumption 48 hours prior to each visit (a standard serving is defined here as 4 oz wine, 12 oz beer, 1 oz spirits)
- •Willing to maintain current use of cannabinoids (if applicable) throughout the study
- •Willing and able to agree to the requirements and restrictions of this study, be willing to give voluntary consent, be able to understand and read the questionnaires, and carry out all study-related procedures
排除标准
- •Individuals who are lactating, pregnant or planning to become pregnant during the study
- •Individual with irregular menstrual cycles (defined as outside 24-38 days cycle range, based on self-reports)
- •Individuals who adhere to a diet (e.g., vegan diet) that restricts consumption of dairy products
- •Has a known sensitivity, intolerability, or allergy to any of the study products or their excipients
- •Weight loss or gain > 3 kg in the 3 months prior to Visit 2 (Day 1)
- •Currently or planning to be on a weight loss regimen during the study
- •Received a vaccine for COVID-19 in the two weeks prior to screening or plans to receive a vaccine for COVID-19 during the study period, currently has COVID-19 or tests positive for COVID-19 within 28 days prior to baseline visit, or currently has any post COVID-19 condition(s) as defined by World Health Organization (WHO) (i.e., individuals with a history of probable or confirmed SARS-CoV-2 infection, usually three months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis)
- •Recent [within 2 weeks of Visit 2 (Day 1)] history of an episode of acute GI illness such as nausea/vomiting or diarrhea
- •Have a history of irritable bowel disease (IBS), inflammatory bowel disease (IBD, including ulcerative colitis and Crohn's disease), functional constipation or diarrhea (defined by the Rome IV diagnostic criteria), celiac disease, malabsorption, gastroparesis, diverticulosis, gastric or duodenal ulcers, pancreatitis, or eating disorder; or have a history of intestinal surgery (excluding appendectomy or herniorrhaphy) or bariatric surgery
- •Have an abnormality or obstruction of the gastrointestinal tract precluding swallowing (e.g., dysphagia) and/or digestion (e.g., history of bowel obstruction)
- •Participated in upper gastrointestinal endoscopy and/or colonoscopy or preparation within 3 months prior to Visit 2 (Day 1)
- •Diagnosed with hypercholesterolemia or hypertriglyceridemia (i.e., elevated fasting low-density lipoprotein (LDL) (≥ 135 mg/dL; ≥ 3.5 mmol/L) or elevated triglycerides (≥ 150 mg/dL; ≥1.7 mmol/L)
- •Has a history of heart disease/cardiovascular disease, uncontrolled hypertension (≥ 140 systolic or ≥ 90 diastolic mmHg), kidney disease (dialysis or renal failure), hepatic impairment or disease
- •Is Type I or Type II diabetic or pre-diabetic [i.e., elevated fasting blood glucose levels (≥ 100 mg/dL; ≥ 5.6 mmol/L) and/or elevated hemoglobin A1c (≥ 6.0%)]
- •Has a history of liver or gallbladder disease or stomach ulcers
- •Has a positive medical history of unstable thyroid disease, previously diagnosed major affective disorder, psychiatric disorder that required hospitalization in the prior year, immune disorders and/or immunocompromised (e.g., HIV/AIDS)
- •Diagnosed with cancer (except localized skin cancer without metastases or in situ cervical cancer) within 5 years prior to the screening visit, or any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential participant at risk because of participation in the study, or influences the results or the potential participant's ability to participate in the study
- •Major surgery in 3 months prior to screening or planned major surgery during the study
- •History of alcohol or substance abuse (including cannabinoids) in the 12 months prior to screening (including having been hospitalized for such in an in-patient or out-patient intervention program)
- •Use of any treatment listed in the study protocol (Section 7.6) outside of the permitted timeframes and/or conditions.
- •Receipt or use of test products in another research study within 30 days prior to Visit 2 or longer if the previous test product is deemed by the investigator to have lasting effects that might influence the eligibility criteria or outcomes of current study
- •Current or previous tobacco use within the last 6 months
- •Self-report of blood donation totaling between 101 mL to 449 mL of blood within 30 days prior to screening or a blood donation of more than 450 mL within 56 days prior to baseline
- •Self-report of donating plasma (e.g., plasmapheresis) within 14 days prior to screening.
- •Any other active or unstable medical conditions or use of medications/supplements/therapies that, in the opinion of the investigator, may adversely affect the participant's ability to complete the study or its measures or pose a significant risk to the participant
结局指标
主要结局
Early (0-2 h) postprandial plasma total amino acid concentration incremental area-under-the-curve (P3 - WHEY vs. placebo treatment)
时间窗: 2 hours
Free leucine, isoleucine, valine, histidine, lysine, methionine, phenylalanine, threonine, tryptophan, arginine, glutamine, glycine, alanine, serine, glutamic acid, aspartic acid, asparagine, tyrosine, cysteine, proline (combined) (µmol·L\^(-1)·120 min)
次要结局
- Total (0-4 h) postprandial plasma essential amino acid concentration incremental area-under-the-curve(4 hours)
- Total (0-4 h) postprandial plasma branched chain amino acid concentration incremental area-under-the-curve(4 hours)
- Total (0-4 h) postprandial plasma peptide YY incremental-area-under-the-curve(4 hours)
- Early (0-2 h) postprandial plasma essential amino acid concentration incremental area-under-the-curve(2 hours)
- Total (0-4 h) postprandial plasma leucine concentration incremental area-under-the-curve(4 hours)
- Postprandial plasma amino acid time to peak concentration(4 hours)
- 8-Item Modified Gastrointestinal Tolerance Questionnaire scores(4 hours)
- Early (0-2 h) postprandial plasma branched chain amino acid concentration incremental area-under-the-curve(2 hours)
- Early (0-2 h) postprandial plasma leucine concentration incremental area-under-the-curve(2 hours)
- Postprandial plasma amino acid concentration, absolute change from baseline to 45 minutes(45 minutes)
- Postprandial plasma amino acid maximum concentration(4 hours)
- Postprandial plasma glucose concentration incremental area-under-the-curve(4 hours)
- Total (0-4 h) postprandial plasma glucagon-like peptide 1 incremental-area-under-the-curve(4 hours)
- Postprandial plasma amino acid concentration, baseline-adjusted change from baseline to 60 minutes(60 minutes)
- Total (0-4 h) postprandial plasma total amino acid concentration incremental area-under-the-curve(4 hours)
- Postprandial plasma amino acid concentration, baseline-adjusted change from baseline to 45 minutes(45 minutes)
- Postprandial plasma amino acid concentration, absolute change from baseline to 60 minutes(60 minutes)
- Postprandial appetite sensation incremental-area-under-the-curve(4 hours)
- 5-Item Palatability Questionnaire scores(4 hours)
- Postprandial plasma insulin concentration incremental area-under-the-curve(4 hours)
- Postprandial appetite sensation scores(4.5 hours)
- Total (0-4 h) postprandial plasma ghrelin incremental-area-under-the-curve(4 hours)
- Ad libitum meal energy intake(4.5 hours)
- Incidence of adverse events(72 days)