Fructose IntoleranceNCT04022434
Investigation of Supplemental L-alanine in the Management of Dietary Fructose Intolerance
A study testing Placedo and Alanine in people with Fructose Intolerance, run by Augusta University at 1 site in United States.
Trial summary
Over the past few decades, fructose consumption has risen significantly in the United States1. This sugar is increasingly being used as a sweetener in a variety of foods1. Because there is a limited absorptive capacity for fructose, excessive ingestion of fructose leads to fructose malabsorption and dietary fructose… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fructose Intolerance
- What is being tested?
- Placedo and Alanine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jan 2014to 30 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- Women of childbearing potential must agree to a urine pregnancy test before supplement is dispensed and to avoid pregnancy throughout the study.
Who cannot join
- Cognitive impairment or any other inability to provide informed consent
- Prisoners
- GI surgery except appendectomy, cholecystectomy, caesarean section, hysterectomy
- Antibiotics in the previous 6 weeks.
- Major co-morbid illnesses, including chronic pancreatitis, celiac disease, inflammatory bowel disease, diabetes, scleroderma, pseudo-obstruction syndromes etc.
- Medication use: opioids, Tegaserod, laxatives, enemas
- Difficulty Swallowing
- Known food allergies or intolerance to any fiber supplements or other dietary nutritional supplements such as: Psyllium (Metamucil), Maltodextrin, Citric Acid, and methylcellulose (Citrucel).
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Augusta University
Augusta, Georgia, 30912
Satish Rao, MD, 706-721-1968, srao@augusta.edu
Helen Smith, 7067211968, hsmith@augusta.edu
About this study
Official title: Investigation of Supplemental L-alanine in the Management of Dietary Fructose Intolerance: a Double-blind, Randomized Study
Over the past few decades, fructose consumption has risen significantly in the United States1. This sugar is increasingly being used as a sweetener in a variety of foods1. Because there is a limited absorptive capacity for fructose, excessive ingestion of fructose leads to fructose malabsorption and dietary fructose intolerance (DFI) 2-9, 13. Incomplete absorption of fructose may lead to a variety of gastrointestinal symptoms, including bloating, pain, gas and diarrhea 2-9. In tertiary care centers, the prevalence of DFI in subjects with unexplained GI symptoms has been estimated to range between 11-50 %, when subjects were assessed with breath tests following administration of 25 grams of fructose 2, 5-7.
Currently, the main treatment for DFI consists of restricting the intake of fructose-containing foods 10-12 or limiting the intake of foods with excess "free fructose" (ie, fructose in excess of glucose) or a high fructan content17. These diet restrictions can improve symptoms in patients with DFI 10-12,17. However, the diet is very restrictive and imposes a significant burden on the individual and the family. In one study, 40% of subjects were unable to comply with dietary restrictions 10. Currently, there are no other therapeutic agents for treating this condition 14, 15. Apart from promoting intestinal fructose absorption, an ideal therapeutic agent should be safe, simple to use, inexpensive and have no calorific value.
Read more
Fructose is mostly absorbed in the small intestine by facilitated diffusion which is mediated by the GLUT-5 transporter protein. This protein is expressed on the intestinal mucosal surface. In the presence of glucose, fructose absorption is increased, mostly due to co-transport with glucose via the GLUT-2 transporter protein. However, the calorie content of glucose precludes its routine use in patients with DFI. Other compounds that promote fructose absorption, such as 3 O-methyl glucose and epidermal growth factor (EGF) have significant side effects and safety issues, making them unsuitable for clinical use in DFI.
Several amino acids, including alanine, have been also been shown to increase intestinal fructose absorption 14. The postulated mechanism is as follows: transmucosal Na+-coupled amino acid transport causes increased water flow through the mucosal apical membrane14. This, in turn, facilitates fructose absorption by a process of 'solvent drag', caused by an increase in intraluminal fructose concentration caused by water removal from the lumen14. The potential benefit of alanine was assessed in a European study in healthy children 14. Ten subjects underwent H2 breath tests following administration of fructose alone (2g/ Kg body weight), followed by a combination of fructose and an equi-molar dose of various amino acids (L-alanine, L-phenylalanine, L-glutamine, L-proline) or glucose. Breath H2 production was assessed as a marker of intestinal fructose absorption. Subjects were asked to report any gastrointestinal symptoms during the test. All subjects had a positive (>20 ppm of H2) breath test (68 ± 38 ppm) with fructose and 6/10 subjects reported either abdominal pain or diarrhea during the test. Co-administration of alanine caused a significant (p < 0.05) decrease in breath H2 production (3 ± 3 ppm), suggesting increased intestinal fructose absorption. Furthermore, none of the subjects reported any gastrointestinal symptoms during the test.
- Conditions
- Fructose Intolerance
- Being tested
- Placedo, Alanine
- Medical subject headings
- Fructose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlacedoDietary supplement
Subjects will mix the placebo in the beverage of their choice and consume this approximately 20 minutes before meals or snacks, in according with the dosing guidelines set for them by the dietitian.
AlanineDietary supplement
Subjects will mix the alanine in the beverage of their choice and consume this approximately 20 minutes before meals or snacks, in according with the dosing guidelines set for them by the dietitian.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Psyllium powder is used as the placebo. A member of the research staff will package and dispense L-alanine and placebo in similar containers. A standard measuring spoon will be provided to the subject for preparing the placebo solution. Subjects will mix the placebo in the beverage of their choice and consume this approximately 20 minutes before meals or snacks, in according with the dosing guidelines set for them by the dietitian.
Meal Placebo Breakfast * 1-2 scoops Snack * .5 - 1 scoop Lunch * 1-2 scoops Snack * .5 - 1 scoop Dinner * 1-2 scoops Receives: Dietary Supplement: Placedo |
| Experimental Alanine | Experimental | L-alanine, USP (Spectrum® Chemicals and Laboratory Products, Gardena, CA) will be packaged and dispensed by one member of the research staff who will have no other role in the study. A one-month supply will be dispensed to the subjects.
Meal L-Alanine Breakfast * 1-2 scoops Snack * .5 - 1 scoop Lunch * 1-2 scoops Snack * .5 - 1 scoop Dinner * 1-2 scoops Receives: Dietary Supplement: Alanine |
What is being measured
The primary outcome is the main question the study is designed to answer.
GI symptom score
Change in GI symptom score with alanine and placebo, when compared to the baseline
Measured: 4 weeks
Secondary outcomes (3)
Fructose consumption
Estimated daily consumption of fructose during the alanine and placebo phases, when compared to the baseline using prospective food diaries
Measured: 4 weeks
Breath hydrogen and methane
Changes in breath hydrogen and/or methane values with alanine and placebo when compared with to the baseline
Measured: 4 weeks
Quality of Life (SF-12)
Changes in SF-12 scores between and after baseline and placebo
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2019
- Study start7 Jan 2014
- Primary completion30 Dec 2020 (estimated)
- Study completion30 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fructose IntoleranceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Augusta University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04022434
- Sponsor's protocol ID
- 611777
- Status last verified
- Jul 2019
- First submitted
- 15 Jul 2019
- Last updated
- 15 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Supplemental L-alanine in the Management of Dietary Fructose Intolerance: a Double-blind, Randomized Study
- ClinicalTrials.gov ID
- NCT04022434
- Acronym / sponsor ID
- 611777
- Conditions
- Fructose Intolerance
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Augusta UniversityUniversity, hospital or other
- Study start
- 7 Jan 2014 (actual)
- Primary completion
- 30 Dec 2020 (estimated)
- Study completion
- 30 Dec 2020 (estimated)
- First posted
- 17 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Over the past few decades, fructose consumption has risen significantly in the United States1. This sugar is increasingly being used as a sweetener in a variety of foods1. Because there is a limited absorptive capacity for fructose, excessive ingestion of fructose leads to fructose malabsorption and dietary fructose intolerance (DFI) 2-9, 13. Incomplete absorption of fructose may lead to a variety of gastrointestinal symptoms, including bloating, pain, gas and diarrhea 2-9. In tertiary care centers, the prevalence of DFI in subjects with unexplained GI symptoms has been estimated to range between 11-50 %, when subjects were assessed with breath tests following administration of 25 grams of fructose 2, 5-7.
Currently, the main treatment for DFI consists of restricting the intake of fructose-containing foods 10-12 or limiting the intake of foods with excess "free fructose" (ie, fructose in excess of glucose) or a high fructan content17. These diet restrictions can improve symptoms in patients with DFI 10-12,17. However, the diet is very restrictive and imposes a significant burden on the individual and the family. In one study, 40% of subjects were unable to comply with dietary restrictions 10. Currently, there are no other therapeutic agents for treating this condition 14, 15. Apart from promoting intestinal fructose absorption, an ideal therapeutic agent should be safe, simple to use, inexpensive and have no calorific value.
Fructose is mostly absorbed in the small intestine by facilitated diffusion which is mediated by the GLUT-5 transporter protein. This protein is expressed on the intestinal mucosal surface. In the presence of glucose, fructose absorption is increased, mostly due to co-transport with glucose via the GLUT-2 transporter protein. However, the calorie content of glucose precludes its routine use in patients with DFI. Other compounds that promote fructose absorption, such as 3 O-methyl glucose and epidermal growth factor (EGF) have significant side effects and safety issues, making them unsuitable for clinical use in DFI.
Several amino acids, including alanine, have been also been shown to increase intestinal fructose absorption 14. The postulated mechanism is as follows: transmucosal Na+-coupled amino acid transport causes increased water flow through the mucosal apical membrane14. This, in turn, facilitates fructose absorption by a process of 'solvent drag', caused by an increase in intraluminal fructose concentration caused by water removal from the lumen14. The potential benefit of alanine was assessed in a European study in healthy children 14. Ten subjects underwent H2 breath tests following administration of fructose alone (2g/ Kg body weight), followed by a combination of fructose and an equi-molar dose of various amino acids (L-alanine, L-phenylalanine, L-glutamine, L-proline) or glucose. Breath H2 production was assessed as a marker of intestinal fructose absorption. Subjects were asked to report any gastrointestinal symptoms during the test. All subjects had a positive (>20 ppm of H2) breath test (68 ± 38 ppm) with fructose and 6/10 subjects reported either abdominal pain or diarrhea during the test. Co-administration of alanine caused a significant (p < 0.05) decrease in breath H2 production (3 ± 3 ppm), suggesting increased intestinal fructose absorption. Furthermore, none of the subjects reported any gastrointestinal symptoms during the test.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Dietary Supplement: PlacedoPsyllium powder is used as the placebo. A member of the research staff will package and dispense L-alanine and placebo in similar containers. A standard measuring spoon will be provided to the subject for preparing the placebo solution. Subjects will mix the placebo in the beverage of their choice and consume this approximately 20 minutes before meals or snacks, in according with the dosing guidelines set for them by the dietitian. Meal Placebo Breakfast * 1-2 scoops Snack * .5 - 1 scoop Lunch * 1-2 scoops Snack * .5 - 1 scoop Dinner * 1-2 scoops |
| Experimental Alanine | Experimental | Dietary Supplement: AlanineL-alanine, USP (Spectrum® Chemicals and Laboratory Products, Gardena, CA) will be packaged and dispensed by one member of the research staff who will have no other role in the study. A one-month supply will be dispensed to the subjects. Meal L-Alanine Breakfast * 1-2 scoops Snack * .5 - 1 scoop Lunch * 1-2 scoops Snack * .5 - 1 scoop Dinner * 1-2 scoops |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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)
- Women of childbearing potential must agree to a urine pregnancy test before supplement is dispensed and to avoid pregnancy throughout the study.
Key exclusion criteria (8 listed)
- Cognitive impairment or any other inability to provide informed consent
- Prisoners
- GI surgery except appendectomy, cholecystectomy, caesarean section, hysterectomy
- Antibiotics in the previous 6 weeks.
- Major co-morbid illnesses, including chronic pancreatitis, celiac disease, inflammatory bowel disease, diabetes, scleroderma, pseudo-obstruction syndromes etc.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlacedoSubjects will mix the placebo in the beverage of their choice and consume this approximately 20 minutes before meals or snacks, in according with the dosing guidelines set for them by the dietitian. | Dietary supplement | Placebo |
| AlanineSubjects will mix the alanine in the beverage of their choice and consume this approximately 20 minutes before meals or snacks, in according with the dosing guidelines set for them by the dietitian. | Dietary supplement | Experimental Alanine |
Primary outcome
GI symptom score
Time frame: 4 weeks
Change in GI symptom score with alanine and placebo, when compared to the baseline
3 secondary outcomes
Fructose consumption
Time frame: 4 weeks
Breath hydrogen and methane
Time frame: 4 weeks
Quality of Life (SF-12)
Time frame: 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2020.
Related trials for Fructose Intolerance
Active, not recruiting
Fructose: Substrate, Stimulus, or Both?
Insulin Resistance, Insulin Sensitivity
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
Recruiting
Ultra-processed Food-reducing Intervention and Continuous Glucose Monitoring
Postprandial Glucose, Glucose Levels
Not yet recruiting
New Microbiota-endocrine Axis in Fructose Malabsorption-caused Visceral Hypersensitivity in Irritable Bowel Syndrome.
Irritable Bowel Syndrome (IBS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Placedo and Alanine in people with Fructose Intolerance, run by Augusta University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Satish Rao, MD (7067211968, srao@augusta.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GI symptom score (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2020.