Folate Absorption Across the Large Intestine

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: 13C5-Calcium-L-Leucovorin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • The Hospital For Sick Chidlren

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy adults
2. Age 18-65 years

Exclusion Criteria

1. <18 years of age, >65 years of age
2. chronic disease (eg. history of hepatic, gastrointestinal, renal, vascular, hematological, or neuropsychiatric disease) or surgery affecting gastrointestinal motility, pH or folate absorption/metabolism
3. 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)
4. regularly consume > 1 drink of alcohol/d or current smoking (last 6 months)
5. planning a pregnancy, pregnant, breast feeding or the use of high-dose oral contraceptives/hormone replacement therapy
6. known sensitivity to Calcium Leucovorin
7. 130mL of blood is > 5% of total blood volume

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Capsule: 400 microg 13C5-Calcium-L-Leucovorin	Drug: 13C5-Calcium-L-Leucovorin; 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.; Other Names: 13C5 Folate
Active Comparator: IV Injection: : 100 microg 13C5-Calcium-L-Leucovorin	Drug: 13C5-Calcium-L-Leucovorin; 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.; Other Names: 13C5 Folate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: University of Florida; Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Deborah O'Connor, MD, The Hospital for Sick Children

Publications and helpful links

General Publications

• Lakoff A, Fazili Z, Aufreiter S, Pfeiffer CM, Connolly B, Gregory JF 3rd, Pencharz PB, O'Connor DL. Folate is absorbed across the human colon: evidence by using enteric-coated caplets containing 13C-labeled [6S]-5-formyltetrahydrofolate. Am J Clin Nutr. 2014 Nov;100(5):1278-86. doi: 10.3945/ajcn.114.091785. Epub 2014 Sep 3.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: July 14, 2009
• First Submitted That Met QC Criteria: July 16, 2009
• First Posted (Estimate): July 17, 2009

Study Record Updates

• Last Update Posted (Estimate): December 31, 2013
• Last Update Submitted That Met QC Criteria: December 30, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: (13C5) Calcium Leucovorin; Folate absorption across the large intestine; Folate Bioavailability
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Protective Agents; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: 1000008487-2b