Investigation of Alanine in Fructose Intolerance: A Dose Ranging Study

Investigation of Alanine in Fructose Intolerance: A Randomized, Double Blind, Dose Ranging, Placebo Controlled Study

Background:

Over the past few decades, fructose is increasingly being used as a sweetener/ additive in a variety of foods. Incomplete absorption of fructose has been implicated as a cause of gastrointestinal symptoms. In tertiary care centers, the prevalence of fructose malabsorption in subjects with unexplained GI symptoms is thought to be between 11-50%, when assessed with breath tests following administration of 25 grams of fructose in a 10% solution. Restriction of dietary fructose has been shown to improve symptoms in these patients to an extent. Currently, there are no therapeutic agents that improve intestinal fructose absorption and thereby decrease symptoms. Studies in the pediatric population have shown that fructose absorption in the small intestine is increased in the presence of glucose or amino acids, especially alanine.

Objective:

The investigators' objective is to assess whether co-administration of an oral solution of L-alanine facilitates fructose absorption and decreases gastrointestinal (GI) symptoms associated with fructose malabsorption in subjects undergoing standard fructose breath test when compared to placebo.

Methods and analysis:

The investigators propose a randomized, double-blind study in 40 subjects with known fructose intolerance. After an overnight fast, each subject will receive an oral solution of 12.5 grams of alanine in 125cc of water or placebo. Next, the subject will receive an oral solution of 25 grams of fructose in a 10% solution. Serum, urine and breath samples will be collected at baseline and at 30-minute intervals for 4 hours. GI symptoms will also be assessed and recorded at 30 minute intervals using a standard questionnaire. Repeated measures ANOVA will be used to compare the data obtained during the study protocol with the baseline (pre-study) data.

Expected outcomes:

Co-administration of alanine with fructose may improve fructose absorption and decrease symptoms in subjects with fructose intolerance.

Hypothesis: Ingestion of alanine along with fructose, will facilitate intestinal absorption of fructose in subjects with fructose malabsorption.

Aim: To investigate the effects of co-administration of equi-molar doses of alanine on a) the absorption of fructose and b) the occurrence of GI symptoms in subjects with fructose malabsorption.

Study Overview

• Status: Recruiting
• Conditions: Fructose Intolerance
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Alanine; Dietary supplement: Alanine

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Satish SC Rao, MD; Phone Number: 319-353-6602; Email: satish-rao@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals and Clinics
      • Contact: Satish SC Rao, MD; Phone Number: 319-353-6602; Email: satish-rao@uiowa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 18-70 years
2. Diagnosis of fructose malabsorption (positive breath test after ingestion of 25 grams of fructose defined as either (a) ≥ 20 ppm rise of breath H2/CH4/both over baseline values or a successive rise of ≥ 5 ppm over baseline and in 3 consecutive breath samples)

Exclusion Criteria:

1. Cognitive impairment or any other inability to provide informed consent
2. Prisoners
3. GI surgery except appendectomy, cholecystectomy, caesarean section, hysterectomy
4. Antibiotics in the previous 3 months
5. Bacterial overgrowth or lactose intolerance
6. Major co-morbid illnesses, including chronic pancreatitis, celiac disease, inflammatory bowel disease, diabetes, scleroderma, pseudo-obstruction syndromes etc.
7. Known food allergies
8. Medication use: opioids, Tegaserod, laxatives, enemas
9. Diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects will receive placebo (mix of sugar and salt).	Dietary supplement: Placebo; Subjects will receive placebo (mix of sugar and salt) 20 minutes before consuming fructose.
Experimental: Alanine - 12.5; Subjects will receive 12.5 grams of alanine	Dietary supplement: Alanine; Subjects will receive 12.5 grams of alanine 20 minutes before consuming fructose.; Dietary supplement: Alanine; Subjects will receive 25 grams of alanine 20 minutes before consuming fructose.
Experimental: Alanine - 25; Subjects will receive 25 grams of alanine.	Dietary supplement: Alanine; Subjects will receive 12.5 grams of alanine 20 minutes before consuming fructose.; Dietary supplement: Alanine; Subjects will receive 25 grams of alanine 20 minutes before consuming fructose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Decrease breath Hydrogen and/or Methane production	less than 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Occurrence or severity of GI symptoms during the test	less than 6 months

Collaborators and Investigators

• Sponsor: Augusta University
• Collaborators: University of Iowa; Teikyo University

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): April 30, 2024

Study Registration Dates

• First Submitted: September 22, 2009
• First Submitted That Met QC Criteria: August 18, 2010
• First Posted (Estimate): August 19, 2010

Study Record Updates

• Last Update Posted (Actual): July 21, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Fructose Metabolism, Inborn Errors; Fructose Intolerance
• Other Study ID Numbers: Fructose: Double Blind