Please select the eligibility criteria that correspond to the clinical trial below.
Title: Investigation of the Effects of a Synbiotic on Liver Fat, Disease Biomarkers and Intestinal Microbiota in Non-alcoholic Fatty Liver Disease
Brief Summary: Non-alcoholic fatty liver disease (NAFLD) is a liver condition in which fat builds up in the liver not caused by alcohol. The liver is an organ that is not designed to build up fat. NAFLD is common in people who have too much body fat in their abdomen or who have diabetes (high blood sugar), but does not always exist with these conditions. NAFLD can also occur in thin people too. NAFLD can be harmful to the liver and may cause the liver to fail over time. NAFLD may also cause adult (or type 2) diabetes and also heart disease. In people who already have diabetes, NAFLD can cause glucose (sugar) levels to be too high.

Our intestines (guts) contain healthy bacteria and some harmful bacteria (bugs). This balance of healthy and harmful bugs is essential for the normal workings of our intestine to digest food. Providing these bacteria do not leak out into the blood they do not cause harm. If the balance of healthy to harmful bugs is upset, the harmful can cause problems and leak out into the blood. Because the liver is connected to the intestine by blood vessels the harmful bacteria can get to the liver and cause problems. These bacteria can cause the liver and the body to build up too much fat and might cause NAFLD and obesity. In this study, we will test the effects of a supplement (synbiotic) taken during the day, that contains a mixture of 'good' healthy bacteria (probiotic) and a sugar (prebiotic) that is not broken down and absorbed into the blood. We will test whether the synbiotic supplement has beneficial effects on the NAFLD liver condition and on factors linked to too much body fat, diabetes and heart disease.


Options:
A: Inclusion Criteria:

* Aged 21 years and older
* Have BMI \>30.0 kg/m2 and \<40 kg/m2
* Willing and able to participate in clinic visits, group sessions, and telephone and Internet communications at specified intervals
* Able to provide data through questionnaires and by telephone
* Willing to maintain contact with the investigators for 12 months
* Willing to allow blood collections
* No known allergy to tree nuts
* Able to be physically active

Exclusion Criteria:

* Diabetic
* Inability to be moderately physically active
* A history or presence of a comorbid diseases for which diet modification and increased physical activity may be contraindicated
* Currently pregnant/breastfeeding
* Planning to become pregnant within the next year
* Currently enrolled in a weight loss program or diet intervention study
* Current use of weight loss medication or supplements
* Planned surgical procedure that can impact the conduct of the study
* Have plans to relocate from area within the next year
* 6+ months use of meds likely to cause weight gain or prevent weight loss
* Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in this study
B: Inclusion Criteria:

* Male or female
* 50 years of age or older
* Residing in the community at baseline (includes assisted living facilities, but excludes long-term care nursing facilities)
* MMSE (Mini-Mental State Examination) at screen of 14-26 (inclusive)
* No medical contraindications to study participation
* Fluent in English or Spanish
* Corrected vision and hearing sufficient for compliance with testing procedures
* Supervision available for study medication
* Caregiver/study partner to accompany participant to all visits
* Study partner must have direct contact with the participant more than 2 days/week
* Able to ingest oral medication
* Daily DHA consumption less than or equal to 200 mg/day in prior two months estimated by an abbreviated DHA food frequency questionnaire
* Neuroimaging consistent with the diagnosis of AD at some time after the onset of the memory decline
* Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator
* Stable use of cholinesterase inhibitors and memantine is permitted if doses are stable for 4 months prior to enrollment

Exclusion Criteria:

* Non-AD dementia
* Residence in a long-term care facility at baseline
* History of clinically significant stroke
* Modified Hachinski Ischemia score ≥ 4
* Current evidence or history in past two years of epilepsy, seizure, focal brain lesion, head injury with loss of consciousness or DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
* Sensory impairment which would prevent subject from participating in or cooperating with the protocol
* Use of another investigational agent within two months
* Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational new drug including clinically significant or unstable hematologic, hepatic, cardiovascular (including history of ventricular fibrillation or ventricular tachycardia), pulmonary, gastrointestinal, endocrine, metabolic, renal, or other systemic disease or laboratory abnormality
* Active neoplastic disease (skin tumors other than melanoma may be included; participants with stable prostate cancer may be included at the discretion of the Project Director)
C: Inclusion Criteria:

* Both men and women
* Age \> 18 years
* Liver fat diagnosed on normal clinical grounds including in most cases liver assessed by Kleiner scoring system to classify severity, with no known aetiological factors for underlying liver disease (e.g. exclusion of hepatitis A, B \& C, primary biliary cirrhosis, autoimmune hepatitis, haemochromatosis). Last liver biopsy will be within 3 years of recruitment to the study.
* Liver fat diagnosed by ultrasound, CT or magnetic resonance imaging (MRI) in patients who also have either diabetes and/or features of the metabolic syndrome, without evidence of known aetiological factors for underlying liver disease (e.g. exclusion of hepatitis A, B \& C, primary biliary cirrhosis, autoimmune hepatitis, haemochromatosis).
* Alcohol consumption ≤ 14 units / week for women ≤ 21 units / week for men.

Exclusion Criteria:

* Alcohol consumption \> 15 units /week for women and \> 22 units /week for men.
* Decompensated acute or chronic liver disease.
* A history of viral hepatitis, diarrhoea, diverticulosis, irritable bowel syndrome, inflammatory bowel diseases, coeliac disease (seropositivity for anti-endomysial immunoglobulin A antibodies; immunoglobulin A (IgA) EMA).
* Previous bariatric or other abdominal surgery.
* Continuous use of antibiotics that may change gut microflora, probiotics, or antisecretory drugs capable of causing achlorhydria within the 2 months preceding enrolment, or evidence of immunoglobulin A or immunoglobulin deficiency (both of which produce confounding effects during assessments of intestinal permeability and small intestinal bacterial overgrowth).
D: Inclusion Criteria:

* Multiple risk factors:

  * diabetes,
  * age =\> 65 years,
  * male sex,
  * hypertension,
  * hypercholesterolemia,
  * smoking,
  * obesity,
  * family history of premature cardiovascular disease;
* Previous manifestations of atherosclerotic disease (ischemic stoke, transient ischemic attack \[TIA\], peripheral artery disease, previous arterial revascularisation procedures, angina pectoris)

Exclusion Criteria:

* Contraindications (known allergies to n-3 PUFA) or indications (previous myocardial infarction) for the treatment with n-3 PUFA
* Serious comorbidity with an unfavourable prognosis over the short term
* Expected non compliance over a long period of time
* Pregnancy

Answer: C