Bacterial Intestinal Gut Modification Around Cancer Surgery (BIG MACS) Diet

Study Overview
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Brief Summary
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The long-term study objective is to develop optimized nutritional therapies for surgery and test them in clinical practice. This pilot study will test a microbiome-optimization diet in colorectal cancer surgery patients. The study hypothesizes that the Bacterial Intestinal Gut Modification Around Cancer Surgery (BIG MACS) Diet will provide participants with increased microbiota accessible carbohydrates (MACs) to support the microbiome and improve outcomes.

Official Title
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Bacterial Intestinal Gut Modification Around Cancer Surgery (BIG MACS) Diet

Conditions
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Dysbiosis, Sarcopenia, Colon Cancer

Intervention / Treatment
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* Dietary Supplement: Standard Diet
* Dietary Supplement: BIG MACS Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 25-70 years Primary diagnosis of colon cancer, stages 1-3. Able and willing to provide informed consent. English-speaking. Willingness to return to the study site for specified study visits at D7 and D30. Able to comply with study measures. Exclusion Criteria: Age ≤ 25 years or ≥70 years If surgery is being performed for any reason other than resection of colon cancer. Neoadjuvant therapy, or if surgery is not the initial approach for the patient's colon cancer treatment Significant anemia (hemoglobin 1.0 g/dL or more below normal range) or history of coagulopathy: any personal history of hereditary or acquired bleeding disorder, or thrombocytopenia with platelets under 100,000. Serum creatinine greater than 1.5 mg/dL. Serum total bilirubin greater than the upper limit of normal in the absence of Gilbert's syndrome or alkaline phosphatase or ALT or AST greater than 2.5 times the upper limit of normal. Elevated INR (1.5 or above). Alcohol intake more than one drink or greater than 20 grams per day for women or 30 grams per day for men. History of gastrointestinal surgery including stomach, small bowel or colon resection, pancreatic surgery, bile duct or gallbladder surgery, or splenectomy, or gastric bypass. History of intra-abdominal sepsis. Previous organ transplantation. Self-reported HIV-positive status, active tuberculosis, active malaria, chronic hepatitis B or C, cirrhosis, or inflammatory bowel disease. Currently pregnant or nursing. History of alcohol, drug, or opioid dependency (excluding nicotine) in the past five years. Active psychosocial or psychiatric problem that is likely to interfere with adherence to the protocol. Depression: A CES-D score more than 16 and a psychologist determining that the patient is not a good fit for surgery. Body mass index (BMI) &lt;20 or &gt; 40 kilograms per meter squared: obesity is known to impact the microbiome and immune system and the occurrence of anastomotic leak, and extreme obesity may confound interpretation of these factors in association to leak. Inferences may be made by matching participants with less severe obesity (BMI &lt;40). Presence of any type of non-MRI compatible implant, including cardiac pacemakers or defibrillators, neurostimulators, cochlear implants, or other metallic hardware Self-reported history of claustrophobia. Incarceration Inability to adhere to the study protocol, procedures, and diet Exclusions may also be made at the discretion of the attending physician.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

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: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Diet<br>Participants receiving only standard of care (SOC) nutrition advice, which is SOC Dietary Instructions, as provided by routine surgical consults and one protein shake per day for 4 weeks prior to surgery (SOC). | Dietary Supplement: Standard Diet<br>* Participants receiving only standard of care (SOC) nutrition advice, which is SOC Dietary Instructions, as provided by routine surgical consults and one protein shake per day for 4 weeks prior to surgery (SOC).<br>|
| Experimental: BIG MACS Diet<br>Participants will be instructed to consume the study diet, referred to as the 'BIG MACS Diet' and one protein shake per day for 4 weeks prior to surgery (SOC). Following surgery, participants will continue to follow the BIG MACS Diet for an additional four weeks, with solid food reintroduction after surgery as early as tolerated. | Dietary Supplement: BIG MACS Diet<br>* Participants will be instructed to consume the study diet, referred to as the 'BIG MACS Diet' and one protein shake per day for 4 weeks prior to surgery (SOC). Following surgery, participants will continue to follow the BIG MACS Diet for an additional four weeks, with solid food reintroduction after surgery as early as tolerated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle mass | The change in muscle mass assessed by MRI-measured area and density of the psoas muscle at the level of the L3 vertebra with adjunct grip strength measurement. | baseline and 4 weeks after surgery | 
| Frequency of accidental gas leakage | this will be assessed in times per day or times per month | 4 weeks after surgery | 
| Frequency of accidental mucus leakage | this will be assessed in times per day or times per month | 4 weeks after surgery | 
| Frequency of accidental liquid stool leakage | this will be assessed in times per day or times per month | 4 weeks after surgery | 
| Frequency of bowel movements | this will be assessed in numbers per day or numbers per week | 4 weeks after surgery | 
| stool consistency | Bristol Stool Chart: Type 1 (hard lumps) through Type 7 (watery, no solid pieces, entirely liquid | 4 weeks after surgery | 
| Bowel emptying patterns | (includes constipation, diarrhea, urgency; range: always--> never) | 4 weeks after surgery | 
| Laxative/stool softener use | Yes/No | 4 weeks after surgery | 
| Laxative/stool softener use | times/day | 4 weeks after surgery | 
| Laxative/stool softener use | times/week | 4 weeks after surgery | 
| Laxative/stool softener use | times/month | 4 weeks after surgery | 
| Gastrointestinal comfort | range: 0 (no problem) --> 4 (very strong discomfort) | 24 hours before surgery | 
| Bowel emptying patterns | includes constipation, diarrhea, urgency; range: 0 (never) --> 4 (always) | 24 hours before surgery | 
| Laxative/stool softener use | range; 0-4+ doses | 24 hours before surgery | 
| Compliance with the dietary intervention or standard of care- Baseline veggie meter | carotenoid score, triplicate measurement; range: 0 (lower estimated value)-800 (arbitrary units; higher estimated value correlates with greater carotenoid concentrations | baseline | 
| Compliance with the dietary intervention or standard of care- Baseline veggie meter | carotenoid score, triplicate measurement; range: 0 (lower estimated value)-800 (arbitrary units; higher estimated value correlates with greater carotenoid concentrations | postop day 7 | 
| Compliance with the dietary intervention or standard of care- Baseline veggie meter | carotenoid score, triplicate measurement; range: 0 (lower estimated value)-800 (arbitrary units; higher estimated value correlates with greater carotenoid concentrations | postop day 30 | 
| Compliance with the dietary intervention or standard of care- survey | 24-hour diet recall surveys conducted by Nutrition Coordinating Center at University of Minnesota | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in microbiome features- alpha diversity | Shannon, Simpson, and Chao1 indices | Baseline, time of surgery, postop day 7 and 30 | 
| Change in microbiome features- beta diversity | compositionally corrected Aitchison's distances | Baseline, time of surgery, postop day 7 and 30 | 
| Fecal metabolites | Targeted fecal and serum metabolomics will measure changes in short chain fatty acids (SCFAs) and bile acids. | baseline and 4 weeks after surgery | 
| Fecal inflammatory markers | ELISA. Fecal calprotectin and IgA levels will be measured using ELISA as markers of intestinal inflammation. | Baseline and 4 weeks after surgery | 
| Changes in body composition- abdominal muscle | total abdominal muscle area in cm squared. Absolute and relative change in total abdominal muscle area per patient over time (cm squared ), with the average change per patient group compared between study and control group | Baseline, time of surgery, postop day 7 and 30 | 
| Changes in body composition- psoas muscle | total psoas muscle area in cm squared. Absolute and relative change in total psoas muscle area per patient over time (cm squared ), with the average change per patient group compared between study and control group | Baseline, time of surgery, postop day 7 and 30 | 
| Changes in body composition- volume of fat | MRI-measured area (cm2) and volume (L) of subcutaneous and visceral adipose tissue | Baseline, time of surgery, postop day 7 and 30 | 
| Changes in body composition- liver fat | MRI-measured liver fat content | Baseline, time of surgery, postop day 7 and 30 |