Folate Absorption Across the Large Intestine

Study Overview
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Brief Summary
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The objective of this study is to determine whether the intact human colon with an unaltered microflora distribution absorbs folate and to what extent it is absorbed into the systemic circulation using a dual/oral intravenous route. This will elicit an understanding of colonic folate absorption and metabolism.

Detailed Description
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This study supplements two earlier in print exploratory studies investigating the absorption of folate across the colon after an infusion during colonoscopy and a pre-trial with the purpose of determining dissolution characteristics of two placebo caplet formulations. Using a dual route oral/intravenous, folate (pharmaceutical name Calcium Leucovorin), labeled with a stable isotope will be used to quantitatively measure total folate levels, as well as the uptake of (13C) labeled folate. A pH dependent caplet targeted to the colon and fluoroscopy will determine dissolution characteristics. Labeled and unlabelled folate in blood and urine samples will be used to quantitatively measure the uptake of folate. This will further our understanding of the kinetics (caplet transit times), colonic folate absorption (metabolism) and impact on folate status (bioavailability) in healthy adults.

Official Title
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Folate Absorption Across the Large Intestine, Study #2: Capsule Study

Conditions
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Healthy

Intervention / Treatment
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* Drug: 13C5-Calcium-L-Leucovorin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults Age 18-65 years Exclusion Criteria <18 years of age, >65 years of age chronic disease (eg. history of hepatic, gastrointestinal, renal, vascular, hematological, or neuropsychiatric disease) or surgery affecting gastrointestinal motility, pH or folate absorption/metabolism regular use of medications affecting gastrointestinal pH, motility or folate absorption/metabolism (eg. anti-acid or nonsteroidal anti-inflammatory drugs [NSAIDS] such as aspirin/ibuprofen, phenytoin, sulfasalazine, phenobarbital, primidone, and cimetidine) regularly consume > 1 drink of alcohol/d or current smoking (last 6 months) planning a pregnancy, pregnant, breast feeding or the use of high-dose oral contraceptives/hormone replacement therapy known sensitivity to Calcium Leucovorin 130mL of blood is > 5% of total blood volume

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Capsule: 400 microg 13C5-Calcium-L-Leucovorin<br> | Drug: 13C5-Calcium-L-Leucovorin<br>* This drug will be used in a clinical trial the objective of which is to determine whether, and to what extent, a physiological concentration of natural folate is absorbed across the large intestine with an intact microflora.<br>* Other names: 13C5 Folate;|
| Active Comparator: IV Injection: : 100 microg 13C5-Calcium-L-Leucovorin<br> | Drug: 13C5-Calcium-L-Leucovorin<br>* This drug will be used in a clinical trial the objective of which is to determine whether, and to what extent, a physiological concentration of natural folate is absorbed across the large intestine with an intact microflora.<br>* Other names: 13C5 Folate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Folate - Study Period 1 |  | Day 1 (Baseline), Day 2 (0h,1h,2h,3h,4h,5h,6h,7h,8h,9h,10h,11h,12h,24hr,48hr) | 
| Blood Folate - Study Period 2 |  | Day 2 (0h, 0.25h,0.5h,1h,1.5h,2h,2.5h,3h,3.5h,4h) | 
| Urine Folate - Study Period 1 |  | 24h, 48h, 72h, 96h | 
| Urine Folate - Study Period 2 |  | 24h, 48h, 72h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dietary Recall Records for folate analysis during urine collection days, Anthropometric. |  | Study Phase 1 (Day 2,Day 3,Day 4,Day 5) Study Period (Day 2,Day 3,Day 4) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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(13C5) Calcium Leucovorin, Folate absorption across the large intestine, Folate Bioavailability