Cardiovascular DiseasePhase 2NCT01131299
Evaluation of Oral Alpha-Cyclodextrin for Decreasing Serum Cholesterol
A Phase 2 study testing Alpha cyclodextrin in people with Cardiovascular Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Disease
- What is being tested?
- Alpha cyclodextrin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Feb 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
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.
Read more
Objectives:
- To determine the effect of oral Alpha-CD on total cholesterol in a nondiabetic population.
Read the 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.
- Conditions
- Cardiovascular Disease
- Being tested
- Placebo, Alpha cyclodextrin
- Keywords
- HDL, Cholesterol, Lipoproteins, Serum Lipids, Alpha-Cyclodextrin, Atherosclerosis, Heart Disease
- Medical subject headings
- Cardiovascular Diseases, Atherosclerosis, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
2 tablets PO 3 times a day for 12-14 weeks
Alpha cyclodextrinDrug
Also called alpha- CD, Alpha-CD
2g PO 3 times a day for 12-14 weeks
| Study group | Role | What they receive |
|---|---|---|
| Alpha cyclodextrin first then placebo | Active comparator | 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). Receives: Other: Placebo; Drug: Alpha cyclodextrin |
| Placebo first then Alpha cyclodextrin | Placebo comparator | 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. Receives: Other: Placebo; Drug: Alpha cyclodextrin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24-28 weeks
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: 24-28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2010 (estimated)
- Study startMar 2010
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Marcelo Amar, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Marcelo J Amar, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01131299
- Sponsor's protocol ID
- 100088
- Other IDs
- 10-H-0088
- Status last verified
- Oct 2016
- First submitted
- 25 May 2010
- Last updated
- 21 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Fedder DO, Koro CE, L'Italien GJ. New National Cholesterol Education Program III guidelines for primary prevention lipid-lowering drug therapy: projected impact on the size, sex, and age distribution of the treatment-eligible population. Circulation. 2002 Jan 15;105(2):152-6. doi: 10.1161/hc0202.101971.
PubMed 11790693Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8.
PubMed 15007110Shepherd J. Dyslipidaemia in diabetic patients: time for a rethink. Diabetes Obes Metab. 2007 Sep;9(5):609-16. doi: 10.1111/j.1463-1326.2006.00642.x.
PubMed 17697054Amar MJ, Kaler M, Courville AB, Shamburek R, Sampson M, Remaley AT. Randomized double blind clinical trial on the effect of oral alpha-cyclodextrin on serum lipids. Lipids Health Dis. 2016 Jul 12;15(1):115. doi: 10.1186/s12944-016-0284-6.
PubMed 27405337
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Oral Alpha-Cyclodextrin for Decreasing Serum Cholesterol
- ClinicalTrials.gov ID
- NCT01131299
- Acronym / sponsor ID
- 100088
- Conditions
- Cardiovascular Disease
- Keywords
- HDL, Cholesterol, Lipoproteins, Serum Lipids, Alpha-Cyclodextrin, Atherosclerosis, Heart Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Mar 2010
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 26 May 2010 (estimated)
- Results
- Posted 21 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alpha cyclodextrin first then placebo | Active comparator | Other: Placebo, Drug: Alpha cyclodextrinRandomized 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). |
| Placebo first then Alpha cyclodextrin | Placebo comparator | Other: Placebo, Drug: Alpha cyclodextrinParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
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 |
|---|---|---|
| Placebo2 tablets PO 3 times a day for 12-14 weeks | Other | Alpha cyclodextrin first then placebo, Placebo first then Alpha cyclodextrin |
| Alpha cyclodextrinAlso: alpha- CD, Alpha-CD2g PO 3 times a day for 12-14 weeks | Drug | Alpha cyclodextrin first then placebo, Placebo first then Alpha cyclodextrin |
Primary outcome
Total Serum Cholesterol Levels for Alpha-cyclodextrin (a-CD) and Placebo Groups After 12-14 Weeks, Compared to Baseline
Time frame: 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.
3 secondary outcomes
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
Time frame: 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
Time frame: 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
Time frame: 24-28 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11790693Fedder DO, Koro CE, L'Italien GJ. New National Cholesterol Education Program III guidelines for primary prevention lipid-lowering drug therapy: projected impact on the size, sex, and age distribution of the treatment-eligible population. Circulation. 2002 Jan 15;105(2):152-6. doi: 10.1161/hc0202.101971.
- Background: PubMed 15007110Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8.
- Background: PubMed 17697054Shepherd J. Dyslipidaemia in diabetic patients: time for a rethink. Diabetes Obes Metab. 2007 Sep;9(5):609-16. doi: 10.1111/j.1463-1326.2006.00642.x.
- Derived from this study: PubMed 27405337Amar MJ, Kaler M, Courville AB, Shamburek R, Sampson M, Remaley AT. Randomized double blind clinical trial on the effect of oral alpha-cyclodextrin on serum lipids. Lipids Health Dis. 2016 Jul 12;15(1):115. doi: 10.1186/s12944-016-0284-6.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Marcelo J Amar, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alpha cyclodextrin in people with Cardiovascular Disease, run by National Heart, Lung, and Blood Institute (NHLBI) 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 11 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: finished, as of the sponsor's last update on 21 Oct 2016. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Serum Cholesterol Levels for Alpha-cyclodextrin (a-CD) and Placebo Groups After 12-14 Weeks, Compared to Baseline (time frame: 24-28 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01131299, which also lists 4 linked publications.
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 21 Oct 2016.