Cardiovascular Disease
Conditions
Keywords
HDL, Cholesterol, Lipoproteins, Serum Lipids, Alpha-Cyclodextrin, Atherosclerosis, Heart Disease
Brief summary
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
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.
Interventions
OTHERPlacebo
2 tablets PO 3 times a day for 12-14 weeks
2g PO 3 times a day for 12-14 weeks
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Serum Cholesterol Levels for Alpha-cyclodextrin (a-CD) and Placebo Groups After 12-14 Weeks, Compared to Baseline | 24-28 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 24-28 weeks | 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. |
| 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 | 24-28 weeks | 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. |
| 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 | 24-28 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
The recruitment occurred at the Clinical Center, NIH.
Pre-assignment details
103 screened participants, 75 completed the study, 14 subject withdrawals and 14 subjects who did not meet inclusion criteria
Participants by arm
| Arm | Count |
|---|---|
| Alpha Cyclodextrin & Placebo Participants Randomized subjects receiving alpha cyclodextrin
Alpha cyclodextrin: 2 g PO 3 times a day for 12- 14 weeks
Randomized subjects receiving placebo comparator
Placebo: 2 tablets PO 3 times a day for 12-14 weeks | 103 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 7 |
Baseline characteristics
| Characteristic | Alpha Cyclodextrin & Placebo Participants |
|---|---|
| Age, Categorical <=18 years | 2 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 99 Participants |
| Region of Enrollment United States | 103 participants |
| Sex: Female, Male Female | 60 Participants |
| Sex: Female, Male Male | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 75 |
| serious Total, serious adverse events | 2 / 75 |
Outcome results
Primary
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.
Time frame: 24-28 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| a-CD | Total Serum Cholesterol Levels for Alpha-cyclodextrin (a-CD) and Placebo Groups After 12-14 Weeks, Compared to Baseline | 180 mg/dL | Standard Error 4 |
| Placebo | Total Serum Cholesterol Levels for Alpha-cyclodextrin (a-CD) and Placebo Groups After 12-14 Weeks, Compared to Baseline | 180 mg/dL | Standard Error 4 |
Comparison: The minimum sample size to detect an 8 mg/dl change in total plasma cholesterol between the placebo and alpha cyclodextrin periods is 62 subjects. The power is 80% by using the normal approximation to a one-sample (paired) two-tail t-test at an alpha of 0.05.p-value: 0.82t-test, 2 sided
Secondary
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.
Time frame: 24-28 weeks
Population: The LIRI score is a composite of six lipoprotein parameters (VLDL, HDL and LDL, and concentrations of large VLDL, large HDL and small LDL subclasses) measured by NMR spectroscopy, which may be apparent years before the onset of overt hyperglycemia. LIRI scores range from zero, the most insulin sensitive, to 100, the most insulin resistant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| a-CD | 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 | 1.4 percentage | Standard Error 0.1 |
| Placebo | 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 | 1.6 percentage | Standard Error 0.1 |
p-value: 0.04t-test, 2 sided
Secondary
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.
Time frame: 24-28 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| a-CD | 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 | 87 mg/dL | Standard Error 0.7 |
| Placebo | 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 | 88 mg/dL | Standard Error 0.9 |
p-value: 0.05t-test, 2 sided
Secondary
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.
Time frame: 24-28 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| a-CD | 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 | 365 nmol/L | Standard Error 35 |
| Placebo | 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 | 405 nmol/L | Standard Error 38 |
p-value: 0.04t-test, 2 sided