Glycemic Response to Two Doses of Low Sugar Apple Juice

Study Overview
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Brief Summary
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Single center, double-blind, randomized controlled cross-over trial with four treatments and four time points. The study has three primary objectives. The first primary objective is to confirm the reduction of postprandial glycemic and insulinemic response after consumption of 500 ml glucose-free apple juice compared to 500 ml untreated apple juice as could be shown in a previous study

Detailed Description
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Single center, double-blind, randomized controlled cross-over trial with four treatments and four time points. The study has three primary objectives. The first primary objective is to confirm the in a previous study shown reduction of postprandial glycemic and insulinemic response after consumption of 500 ml glucose-free apple juice compared to 500 ml untreated apple juice. The second primary objective is to show the reduction of postprandial glycemic response after consumption of 250 ml glucose-free apple juice compared to 250 ml untreated apple juice. The third primary objective is to show the reduction of insulinemic response after consumption of 250 ml glucose-free apple juice compared to 250 ml untreated apple juice. Secondary objectives include safety aspects, specifically the occurrence of diarrhoea in all four treatment groups, differences between treatment groups on the Bristol Stool Forms Scale, gastro-intestinal symptoms and laboratory parameters. In addition, gluconate excretion and excreted portion of ingested gluconate are of interest as well as faecal pH.

Official Title
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Double-blind, Randomized, Controlled, Four Treatment Four Period Cross-over Trial on Glycemic Response, Excretion of Gluconate and Tolerability of Two Doses of Low Sugar Apple Juice

Conditions
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Prediabetes

Intervention / Treatment
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* Other: 500 ml glucose-depleted apple juice
* Other: 500 ml conventional apple juice
* Other: 250 ml glucose-depleted apple juice
* Other: 250 ml conventional apple juice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males aged ≥ 18y Impaired fasting glucose (IFG) Written informed consent Consent to collect stools and urine four times for three days Exclusion Criteria: Subjects currently enrolled in another clinical study Subjects having finished another clinical study within the last 4 weeks before inclusion. Subjects having participated in the study HB-RCT1-2015 Hypersensitivity, allergy or idiosyncratic reaction to apple, apple juice or other apple containing food Acute or chronic infections Renal insufficiency Gastrointestinal illness No stools of type 5-7 of Bristol Stool Form Scale within the last week before inclusion History of gastrointestinal surgery Known fructose intolerance Overt diabetes mellitus Endocrine disorders Any disease or condition which might compromise significantly the hematopoietic, renal, endocrine, pulmonary, hepatic, cardiovascular, immunological, central nervous, dermatological or any other body system with the exception of the conditions defined by the inclusion criteria History of hepatitis B and C History of HIV infection History of coagulation disorders or pharmaceutical anti-coagulation (with the exception of acetylsalicylic acid) Regular medical treatment including OTC, which may have impact on the study aims (e.g. gluconic acid-containing OTCs, antidiabetic drugs, laxatives etc.) Major cognitive or psychiatric disorders Subjects who are scheduled to undergo hospitalization during the study period Eating disorders (e.g. anorexia, bulimia) or special diets (e.g. vegan, vegetarian) Present drug abuse or alcoholism Legal incapacity

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: a double-blind randomised controlled cross-over trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: verum 500<br>500 ml low sugar apple juice manufactured from conventional apple juice via a series of enzymatic reactions that end up in a final content of free glucose less than 0,5 g/l. | Other: 500 ml glucose-depleted apple juice<br> <br> |
| Placebo Comparator: control 500<br>500 ml conventional apple juice produced by a general apple juice production process (free glucose 17g/l) | Other: 500 ml conventional apple juice<br> <br> |
| Active Comparator: verum 250<br>250 ml low sugar apple juice manufactured from conventional apple juice via a series of enzymatic reactions that end up in a final content of free glucose less than 0,5 g/l. | Other: 250 ml glucose-depleted apple juice<br> <br> |
| Placebo Comparator: control 250<br>250 ml conventional apple juice produced by a general apple juice production process (free glucose 17g/l) | Other: 250 ml conventional apple juice<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| iAUC glucose 500 | Incremental AUC (iAUC120) of blood glucose levels (according to FAO/WHO) after 500 ml juice | 120 min after ingestion | 
| iAUC insulin 500 | iAUC insulin 500 | 120 min after ingestion | 
| iAUC glucose 250 | Incremental AUC (iAUC120) of blood glucose levels (according to FAO/WHO) after 250 ml juice | 120 min after ingestion | 
| iAUC insulin 250 | iAUC insulin 250 | 120 min after ingestion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| diarrhea | Occurrence of diarrhoea as assessed by stool frequency and Bristol Stool Forms Scale (Lewis, 1997) (3 or more loose or liquid stools per day, definition according to the WHO) | before and 60 and 120 minutes after ingestion with respect to the last 2 hours | 
| gastro-intestinal symptoms | Assessed by completing questionnaires on gastrointestinal symptoms (GSRS; Svedlund 1988; Dimenäs 1995; Revicki 1998) | before and 60 and 120 minutes after ingestion with respect to the last 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glycemic response, enzymatic conversion, gluconate