Evaluation of Oral Alpha-Cyclodextrin for Decreasing Serum Cholesterol

Study Overview
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Brief Summary
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Background: Cardiovascular disease (CVD) is a leading cause of death in developed countries. Although statin-type drugs are currently the most effective therapeutic agents for reducing CVD risk. One possible complementary approach involves the use of soluble dietary fibers that are known to reduce blood cholesterol levels. However, analysis has shown that most soluble fibers reduce total cholesterol levels by relatively small amounts. Alpha-Cyclodextrin (Alpha-CD), also sold in commerical form, is a soluble fiber derived from corn that is used as an ingredient in many foods, such as bread rolls, crackers, juices, and reduced fat spreads. It is added to food primarily as a fiber supplement but is also used to stabilize flavors, colors, vitamins, and fatty acids. Studies in animals and humans have shown that Alpha-CD may help to improve insulin resistance and lower LDL cholesterol levels with no apparent side effects. More research is needed to determine the effect of Alpha-CD on total cholesterol levels in healthy volunteers. Objectives: - To determine the effect of oral Alpha-CD on total cholesterol in a nondiabetic population.

Detailed Description
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This single center, double-blinded, cross-over, placebo controlled clinical pilot study will investigate the effectiveness of a soluble dietary fiber, alpha-cyclodextrin (alpha-CD), on blood lipid and lipoprotein levels in healthy human subjects. alpha-CD, a cyclical polymer of glucose, is currently sold as an over the counter food supplement and is a common ingredient in many foods. This is the first study that will evaluate the effect of alpha-CD in healthy subjects. One gram of alpha-CD has been shown to bind as much as 9 grams of dietary fat, and like other soluble dietary fibers or bile acid sequestrants (BAS) it may decrease the intestinal absorption of fats, which has been shown to reduce the incidence of cardiovascular disease (CVD). Animal studies in our laboratory have shown that oral alpha-CD lowers Low Density Lipoprotein-cholesterol (LDL-C) by approximately 15 percent in mice on a high fat diet. Other clinical trials utilizing this compound showed that it is a safe therapy with no significant side effects. Eligibility: - Individuals between 18 and 75 years of age who do not have type 1 or type 2 diabetes. Design: This study will require three visits to the NIH Clinical Center. At the first visit, participants will provide information about current diet and exercise routines, and will have a physical examination with blood and urine tests. At the end of this visit, participants will be randomized to receive either Alpha-CD or placebo, and will be asked to take two 1 gram tablets three times a day, anytime from 1 hour before to the end of each meal. Participants will take a total of six tablets per day for 12 weeks. At the end of the first 12 weeks, participants will return to the clinical center for another interview and examination, and blood and urine tests. At the end of this visit, participants will receive the treatment not given in the first part of the study (either Alpha-CD or placebo), and will take tablets on the same schedule as before for 12 more weeks. Participants will wait for 1 week after stopping the previous study prescription before starting the next one. At the end of the second 12 weeks, participants will have a final interview and examination with blood and urine tests. Participants will be asked to keep 7-day food records before each clinic visit to be collected at the second and third visits. A short physical activity assessment will be collected at each visit to review any changes in physical activity.

Official Title
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Evaluation of Oral Alpha-Cyclodextrin for Decreasing Serum Cholesterol

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Other: Placebo
* Drug: Alpha cyclodextrin


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Males and females between the ages of 18-75. Subject understands protocol and provides written, informed consent in addition to a willingness to comply with specified follow-up evaluations. EXCLUSION CRITERIA: Pregnancy or women currently breastfeeding. BMI less than 18.5 Subjects with unstable weight that varies greater than 10% over the past 3 months. Subjects currently following any low-fat (< 20%) diet. Subjects that routinely consume less than 3 meals/snacks per day Subjects taking the following medications, which may show reduced absorption with alpha-CD or may otherwise interfere with the study will be excluded: soluble fiber supplements, BAS, plant sterol supplements, antibiotics, anticoagulants, anticonvulsants, antiarrhythmics , cyclosporine, mycophenolate, synthroid, vitamin A, E and K and or any drug that is necessary to take with a meal. If any of these medications are initiated during the study, the subjects will be instructed to discontinue the use of the alpha-CD or placebo pills and to withdraw from the study. Short-term and prophylactic antibiotics may be taken during study participation for up to 14 days, at least 2 hours apart from the study drug. Subjects with chronic diarrhea, gastric bypass or lap-band procedures, ostomies, bowel motility problems, or other conditions that could affect intestinal fat absorption. Subjects initiating new medications or patients on multiple medications may also be excluded. Patients with type I or type II diabetes. Subjects currently taking alpha-CD in its commercial form. Volunteers may also be excluded, if in the opinion of the study investigators, they have some other condition or disorder that may adversely affect the outcome of the study or the safety of the volunteer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alpha cyclodextrin first then placebo<br>Randomized subjects will receive alpha cyclodextrin 2g orally three times a day for 12-14 weeks. After the one week washout, the subjects will receive 2 tablets orally of placebo (three times a day for 12-14 weeks). | Other: Placebo<br>* 2 tablets PO 3 times a day for 12-14 weeks<br>Drug: Alpha cyclodextrin<br>* 2g PO 3 times a day for 12-14 weeks<br>* Other names: Alpha-CD;|
| Placebo Comparator: Placebo first then Alpha cyclodextrin<br>Participants will receive 2 tablets orally of placebo (three times a day for 12-14 weeks). The subjects will have a one-week washout. After the washout, the participants will receive alpha cyclodextrin 2g orally three times a day for 12-14 weeks. | Other: Placebo<br>* 2 tablets PO 3 times a day for 12-14 weeks<br>Drug: Alpha cyclodextrin<br>* 2g PO 3 times a day for 12-14 weeks<br>* Other names: Alpha-CD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Serum Cholesterol Levels for Alpha-cyclodextrin (a-CD) and Placebo Groups After 12-14 Weeks, Compared to Baseline | Total cholesterol levels were measured at the end of each study arm (a-CD or placebo). a-CD (2g) was taken orally three times a day for 12-14 weeks. Placebo (2 tablets) was taken orally for 12-14 weeks. There was a one-week washout period between each arm. | 24-28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Small LDL Particle Number (by NMR Spectrometry of Lipoproteins) After 12-14 Weeks Intervention, Compared to Baseline for Alpha-cyclodextrin (a-CD) and Placebo Groups After 12-14 Weeks, Compared to Baseline | Small LDL particle numbers were measured at the end of each study arm (a-CD or placebo). a-CD (2g) was taken orally three times a day for 12-14 weeks. Placebo (2 tablets) was taken orally for 12-14 weeks. There was a one-week washout period between each arm. | 24-28 weeks | 
| Serum Glucose Levels After 12-14 Weeks Intervention, Compared to Baseline for Alpha-cyclodextrin (a-CD) and Placebo Groups After 12-14 Weeks, Compared to Baseline | Serum glucose levels was measured at the end of each study arm (a-CD or placebo). a-CD (2g) was taken orally three times a day for 12-14 weeks. Placebo (2 tablets) was taken orally for 12-14 weeks. There was a one-week washout period between each arm. | 24-28 weeks | 
| Lipoprotein Insulin Resistance Index (LIRI) After 12-14 Weeks Intervention, Compared to Baseline for Alpha-cyclodextrin (a-CD) and Placebo Groups After 12-14 Weeks, Compared to Baseline | LIRI was measured at the end of each study arm (a-CD or placebo). a-CD (2g) was taken orally three times a day for 12-14 weeks. Placebo (2 tablets) was taken orally for 12-14 weeks. There was a one-week washout period between each arm. | 24-28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HDL, Cholesterol, Lipoproteins, Serum Lipids, Alpha-Cyclodextrin, Atherosclerosis, Heart Disease