The Effects of Calcium in Conjunction With Multi-mineral Supplementation (Aquamin) on Gut Microbes and Microbially-derived Metabolites in Subjects at Risk for Colon Cancer in a Randomized Controlled Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Biomarkers of Risk for Colorectal Cancer
研究概览
简要总结
In the proposed study, investigators will conduct a 90-day dietary intervention study in human subjects. Thirty individuals at risk for adenomatous colon polyp formation will be randomized to receive a calcium and multi-mineral-rich natural product (Aquamin) or a comparable level of calcium alone. There will also be a placebo group. Prior to ingesting the study agents and following the course of treatment, colonic biopsies will be obtained by sigmoidoscopy and quantitatively examined for markers of growth and differentiation. In this study, metabolomic and microbial profiles will also be generated from fecal and colon mucosal samples taken at baseline and study endpoint.
详细描述
The purpose of this study is to see what effects a calcium-rich, multi-mineral-rich natural product, Aquamin®, derived from marine algae, has compared to calcium alone or a sugar pill (placebo). Investigators are looking at whether these supplements do anything to the cell lining of the colon. Specifically, to see if Aquamin®, calcium, or placebo (sugar pill) change markers of cell growth and differentiation (or "biomarkers") in the cells of the colon. The natural product, Aquamin®, contains calcium but, in addition, has a significant amount of magnesium and measurable levels of approximately 70 different trace elements (essentially, everything the algae can accumulate from seawater). Aquamin is a product that is marketed for the fortification of food, beverage, and supplement products. In this study, it is being used for research and therefore, its use is investigational. Calcium supplements have been shown to reduce colonic polyps (precursor lesions to colon cancer). This study will NOT look at polyp formation in the colon, but only at biomarkers of colon cell growth and function. If investigators find that the multi-mineral natural product is substantially more effective than calcium alone in changing these biomarkers, it is possible that a larger study could be conducted that is intended to study colon polyp prevention. In order to test these ideas investigators need to compare the supplement Aquamin®, to something already tested (calcium) and a placebo (sugar pill) to see if any changes are related to the supplements or just naturally happen.
There is increasing recognition that dietary or environmental predispositions to colorectal cancer may be mediated at least in part by alterations of gut microbial composition and metabolomic profiles. Human gut microbiota are now recognized to play an important role in host health and changes in the composition of gut microbial communities have been linked with metabolic alterations that affect colorectal cancer risk. Investigators have previously established that dietary supplementation can correlate with metabolic or microbial alterations in their most recent long-term study in mice on high-fat western diet (HFWD) and calcium. Investigators had also demonstrated that Aquamin-supplemented mice had significantly decreased liver and colon tumors. Based on these studies, investigators anticipate that Aquamin will improve the gut microbial composition and alter the metabolomic profile in these subjects.
If participant agree to participate in this research study, he/she will be asked to sign this informed consent document before any tests are performed or data collected. This research study consists of three time periods (phases): a pre-treatment period; a study treatment period; and an end-of-study treatment period. The study requires three visits to the University of Michigan's Clinical Research Unit (MCRU). These are referred to as the Screening Visit, Baseline Visit and Final Visit.
After participants are determined to meet eligibility requirements, they will be randomized as to which product they will receive. Randomization is like a flip of a coin. A participant will have an equal chance (33.3%) of being given one of three assignments: a multi-mineral natural product (Aquamin®); a calcium-only supplement; or a placebo ("sugar pill"). Each participant will be required to take four capsules per day (two taken in the morning and two in the evening) for 90 days. Neither they nor the study team investigators will know which product they are receiving. That information will be kept in the hands of the pharmacist who dispenses the agent that participant will take.
- Each participant will be given a physical examination, which will include measurements of his/her height, weight, and vital signs (temperature, blood pressure, heart rate, breathing rate).
- The study nurse or physician's assistant will review participant's past medical history.
- Participants will be asked about any other medical conditions that they may have and all medication(s) they are currently taking. It is important that participants tell the study personnel about any medications they are taking including over-the-counter medications, calcium supplements with or without vitamin D, other vitamins, herbal medications and alternative medicines. Participants may need to stop some of their medicines in order to participate in this study. Participants are instructed to inform study personnel at any time during the study participation if they begin to take any medication(s).
- Study participants will be asked about their intake of foods and supplements containing calcium and vitamin D.
- Participants will be asked to provide information regarding their usual food that they eat (over a year), past year diet history questionnaire (DHQ II)
- Participants will be asked to take a pregnancy test within 14 days before the start of the study if she is a woman able to become pregnant.
- Participants will be asked to not take calcium, vitamin D, fiber, ginger, or fish oil supplements (including multivitamins that have low amounts) for 14 days before the study begins and for 90 days after the study begins.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be able to give written informed consent.
- •Be generally healthy, male or female, ages 18 to 80 years old.
- •Must have one of the following:
- •i)A first degree relative (father/mother, son/daughter, brother/sister) with colorectal cancer under the age of 60 at the time of diagnosis; OR ii)Participant have had a colorectal polyp. OR iii)Participant have previously had removed early stage colon cancer (stage I or II removed surgically and without recommendation for adjuvant therapy or with stage III colorectal cancer (CRC) treated with curative surgery >5 years ago). iv)Pre-menopausal women with intact female reproductive organs must have a negative pregnancy test within 2 weeks of the baseline flexible sigmoidoscopy. Post-menopausal is defined as no menses for the previous 12 months. If cessation of menses is within 12 months then the subject should be treated as pre-menopausal and a pregnancy test performed.
排除标准
- •Must not be pregnant or lactating women and women of child bearing potential unwilling to use acceptable birth control throughout the study.
- •Participants must not have a history or diagnosis of any of the following conditions:
- •i)Kidney disease, including kidney "stones" or hypercalcemia. ii)Crohn's disease, or inflammatory bowel disease. iii)Any stomach or intestinal bleeding disorders (gastrointestinal bleeding from gastric or duodenal ulcers, or gastrin secreting tumors) or active gastric / duodenal ulcers - peptic ulcer disease (without bleeding in last 3 months). iv)Coagulopathy/hereditary hemorrhagic disorders/ or receiving therapeutic doses of Coumadin or heparin. v)Hereditary and familial polyposis (HNPCC/ familial adenomatous polyposis (FAP); Lynch Syndrome) because these are rare conditions with unique etiology.
- •Participants will be excluded if they have taken the following, within the last 14 days or are unwilling to forgo the following for 14 days prior to entry into the study:
- •i)Calcium, Vitamin D, ginger, or fish oil supplements, including multivitamins that have low amounts of calcium/Vitamin D and fiber supplements. ii)Non-steroidal anti-inflammatory medications (NSAIDS), such as Aspirin or Ibuprofen (except for occasional pain control or low dose aspirin for cardiovascular disease prevention). iii)Corticosteroids (a type of steroid drug such as prednisone or cortisol that helps your body to regulate your stress response, immune response and inflammation). iv)Cephalosporin antibiotics (e.g., rocephin, keflex, omnicef).
研究组 & 干预措施
Aquamin®
Experimental: Aquamin® (4 capsules per day) - 4 capsules; 2 to be taken in the morning and 2 in the evening
干预措施: Aquamin® (Drug)
Calcium Carbonate
Active Comparator: Calcium Carbonate (4 capsules per day) - 4 capsules; 2 to be taken in the morning and 2 in the evening
干预措施: Calcium Carbonate (Drug)
Placebo
Placebo (Maltodextrin) - 4 capsules; 2 to be taken in the morning and 2 in the evening
干预措施: Placebo (Drug)
结局指标
主要结局
Biomarkers of Risk for Colorectal Cancer
时间窗: 90 days
A panel of biomarkers of risk for colorectal cancer in colonic mucosal biopsies of normal appearing tissue: proliferation marker (Ki67), differentiation markers (E-cadherin, AE1/AE3 and cytokeratin \[CK 20\]), β-catenin, extracellular calcium-sensing receptor (CaSR), Caspase-3, bax and survivin assessed by quantitative immunohistology. The purpose is to compare growth, differentiation and apoptosis biomarkers, pre and post intervention.
Colonic-mucosal Associated Microbial Profile.
时间窗: 90 days
In colonic mucosa and stool samples: Microbial analysis will be performed on colonic mucosa and stool samples. This analysis will show the difference in microbial communities before and after the intervention.
Colonic-mucosal Associated Metabolomic Profile.
时间窗: 90 days
In serum, colonic mucosa and stool samples: Metabolomic (targeted and untargeted) profile will be assessed in serum, stool and colonic mucosal biopsies. These analyses will show the difference in the metabolomic profile before and after the intervention.
次要结局
- Biomarkers of bone turnover / metabolism.(90 days)
- Biomarkers of liver function(90 days)
研究者
James Varani
Professor of Pathology
University of Michigan