LipoidosisPhase 2NCT00045812
SCH-58235 (Ezetimibe) to Treat Homozygous Sitosterolemia
A Phase 2 study testing SCH-58235 in people with Lipoidosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will test the safety and effectiveness of SCH-58235 (Ezetimibe) in lowering sitosterol, plant sterol and cholesterol blood levels in patients with homozygous sitosterolemia when added to the patients' current treatment regimen. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Lipoidosis
- What is being tested?
- SCH-58235
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2001to Apr 2004
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female, age greater than or equal to 10 years are eligible.
- Patients must have a diagnosis of homozygous sitosterolemia with an elevated plasma sitosterol level (greater than 5 mg/dL at screening visit) on their current regimen.
- All women of childbearing potential must be practicing an effective method of contraception.
- All women of childbearing potential must have a negative urine pregnancy test within 72 hours prior to the start of the study medication.
- Patients must not have any condition which, in the opinion of the investigator, would be likely to render the patient unable to complete the study or for which study participation would produce significant risk or not be in the best interests of the patient.
- Individual with poor mental function, drug or substance abuse, or individuals with unstable psychiatric illness, which, in the opinion of the investigator, may interfere with optimal participation in the study will be excluded.
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- Women must not be pregnant or lactating.
- Patients must not have had treatment with any other investigational drug within 30 days prior to visit 1.
- Patients can not newly diagnosed or untreated person who has not been given an opportunity to consider treatment with standard of care and an opportunity to decline such treatment.
- Patients must not have congestive heart failure NYHA class III or IV.
- Patients must not have uncontrolled cardiac arrhythmias.
- Patients must not have had a myocardial infarction, coronary bypass surgery or angioplasty within 6 months of the screening visit (Visit 1).
- Patients must not have unstable angina pectoris or unstable or severe peripheral vascular disease.
- Patients must not have uncontrolled diabetes mellitus (Hb(A1c) greater than 10%). Patients with diabetes mellitus should be on a stable antihyperglycemic regimen for at least 4 weeks prior to the screening visit (Visit 1).
- Patients must not have uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins. Clinically euthyroid patients on stable replacement doses of thyroid hormone (on the same dose for at least 4 weeks prior to study entry and with TSH equal to 10 IU/mL) are eligible for enrollment.
- Patients must not have uncontrolled hypertension (systolic BP greater than 200 mm Hg and/or diastolic BP greater than 110 mm Hg).
- Patients must not have creatinine greater than 2.0 mg/dL at the screening visit (Visit 1), or active renal disease with significant proteinuria (greater than 1 albumin/mg creatinine).
- Patients must not have active acute or chronic hepatobiliary disease; AST or ALT greater than 5 times the upper limit of normal of the reference laboratory at the screening visit (Visit 1).
- Patients must not have disorders of the hematologic, digestive (including malabsorptive disorders), or central nervous system including cerebrovascular disease and degenerative diseases that would limit study evaluation or participation.
- Patients must not be HIV positive.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, 20892
About this study
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate SCH-58235 in Homozygous Sitosterolemia
This study will test the safety and effectiveness of SCH-58235 (Ezetimibe) in lowering sitosterol, plant sterol and cholesterol blood levels in patients with homozygous sitosterolemia when added to the patients' current treatment regimen. Homozygous sitosterolemia is an inherited disorder of sterol metabolism in which an excess of many plant sterols, including sitosterol, is absorbed and not enough excreted. (Sterols are substances used to form hormones, vitamins and membranes found in animal and plant lipids.). Patients can develop atherosclerosis with coronary heart disease as early as childhood, as well as other problems including arthritis, arthralgia, and tendon xanthomas (lipid deposits). Current sitosterolemia treatments may include a low sterol diet, medications, intestinal surgery, or a combination of these. Ezetimibe is a member of a new class of drugs called "specific cholesterol absorption inhibitors" that may lower cholesterol, sitosterol and other plant sterol blood levels.
Patients with homozygous sitosterolemia 10 years of age and older may be eligible for this study. Participants will have a medical history and physical examination and will be randomly assigned to one of two treatment groups. One group, which will include about 80 percent of all study participants, will take 10 mg of Ezetimibe a day, and the second group (20 percent of participants) will take a placebo (an inactive look-a-like pill).
Read more
Patients will have 7 clinic visits during the 12-week study, when some or all of the following procedures and tests will be done:
- Measurement of vital signs (heart rate, blood pressure, breathing rate and temperature)
- Dietary maintenance - interview about how well that patient is adhering to the diet
- Medication review - interview about other medications the patient is taking
- Blood draw for tests
- Urine sample for tests
- Pregnancy test for women of childbearing potential
- Electrocardiogram (ECG) to measure the electrical activity of the heart
- Blood draw to determine sitosterol, other plant sterol levels, and lipid levels (cholesterol and other blood lipid concentrations)
- Xanthoma measurement (with a ruler and X-ray of the foot)
Read the detailed description
Homozygous sitosterolemia is an autosomally inherited recessive disorder of sterol metabolism. Patients with homozygous sitosterolemia can present with accelerated atherosclerosis with initial CHD events occurring in childhood. In addition, these patients can have tendon xanthomas, hemolytic episodes, as well as arthritis and arthralgias. Plasma levels of sitosterol and other dietary sterols are markedly elevated in homozygous sitosterolemic patients, and are diagnostic of this disorder. A low sterol diet provides only limited reduction in sitosterol levels and currently available medical treatments, such as bile salt binding resins, are usually insufficiently effective or poorly tolerated.
SCH-58235 is a member of a new class of therapeutic agents, specific cholesterol absorption inhibitors, being developed to treat hypercholesterolemia. Preclinical animal studies and clinical studies in humans have demonstrated significant reductions in serum cholesterol levels with SCH-58235 treatment. In the current study, the efficacy and safety of SCH-58235 will be studied in patients with homozygous sitosterolemia, an inherited condition in which a wide range of plant sterols, including sitosterol, are excessively absorbed and inadequately excreted, leading to dramatic increases in tissue deposition. SCH-58235 may lower sitosterol levels by directly inhibiting sitosterol absorption (since plant sterols and cholesterol are structurally similar sterols) and/or by inhibiting cholesterol absorption and indirectly by increasing hepatic uptake of plasma LDL with increased cholesterol and sitosterol excretion. These mechanisms of action could lead to reductions in both plant sterol and LDL cholesterol levels in these patients, thereby providing important clinical benefits. The current study will determine if SCH-58235 will be safe and well tolerated and provide significant reductions in plant sterols (plasma sitosterol and campesterol) and low-density lipoprotein-cholesterol (LDL-C) concentrations in patients with homozygous sitosterolemia.
This is a multicenter, randomized, double-blind, placebo-controlled study lasting 12 weeks. Patients with a diagnosis of homozygous sitosterolemia who have an elevated plasma sitosterol level on their current regimen will be studied. Patients will be eligible to enroll in the study whether their current regimen is medication(s), surgical (prior ileal bypass), apheresis, a combination of treatments, or no active regimen. The primary objective of this study is to evaluate the efficacy and safety of 10 mg/day of SCH-58235 in patients with homozygous sitosterolemia who continue to have an elevated plasma sitosterol level.
- Conditions
- Lipoidosis
- Being tested
- SCH-58235
- Keywords
- Cholesterol, Sitosterol, Atherosclerosis, Intestine, Absorption, Homozygous Sitosterolemia, Sterol Metabolism
- Medical subject headings
- Lipidoses, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SCH-58235Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2002 (estimated)
- Study startMar 2001
- Study completionApr 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for LipoidosisStudies 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
- Enrolment
- 5 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00045812
- Sponsor's protocol ID
- 010115
- Other IDs
- 01-H-0115
- Status last verified
- Apr 2004
- First submitted
- 10 Sep 2002
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Salen G, Shefer S, Nguyen L, Ness GC, Tint GS, Shore V. Sitosterolemia. J Lipid Res. 1992 Jul;33(7):945-55.
PubMed 1431587Bhattacharyya AK, Connor WE, Lin DS, McMurry MM, Shulman RS. Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis. Arterioscler Thromb. 1991 Sep-Oct;11(5):1287-94. doi: 10.1161/01.atv.11.5.1287.
PubMed 1911714
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate SCH-58235 in Homozygous Sitosterolemia
- ClinicalTrials.gov ID
- NCT00045812
- Acronym / sponsor ID
- 010115
- Conditions
- Lipoidosis
- Keywords
- Cholesterol, Sitosterol, Atherosclerosis, Intestine, Absorption, Homozygous Sitosterolemia, Sterol Metabolism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Mar 2001
- Study completion
- Apr 2004
- First posted
- 11 Sep 2002 (estimated)
- 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.
This study will test the safety and effectiveness of SCH-58235 (Ezetimibe) in lowering sitosterol, plant sterol and cholesterol blood levels in patients with homozygous sitosterolemia when added to the patients' current treatment regimen. Homozygous sitosterolemia is an inherited disorder of sterol metabolism in which an excess of many plant sterols, including sitosterol, is absorbed and not enough excreted. (Sterols are substances used to form hormones, vitamins and membranes found in animal and plant lipids.). Patients can develop atherosclerosis with coronary heart disease as early as childhood, as well as other problems including arthritis, arthralgia, and tendon xanthomas (lipid deposits). Current sitosterolemia treatments may include a low sterol diet, medications, intestinal surgery, or a combination of these. Ezetimibe is a member of a new class of drugs called "specific cholesterol absorption inhibitors" that may lower cholesterol, sitosterol and other plant sterol blood levels.
Patients with homozygous sitosterolemia 10 years of age and older may be eligible for this study. Participants will have a medical history and physical examination and will be randomly assigned to one of two treatment groups. One group, which will include about 80 percent of all study participants, will take 10 mg of Ezetimibe a day, and the second group (20 percent of participants) will take a placebo (an inactive look-a-like pill).
Patients will have 7 clinic visits during the 12-week study, when some or all of the following procedures and tests will be done:
- Measurement of vital signs (heart rate, blood pressure, breathing rate and temperature)
- Dietary maintenance - interview about how well that patient is adhering to the diet
- Medication review - interview about other medications the patient is taking
- Blood draw for tests
- Urine sample for tests
- Pregnancy test for women of childbearing potential
- Electrocardiogram (ECG) to measure the electrical activity of the heart
- Blood draw to determine sitosterol, other plant sterol levels, and lipid levels (cholesterol and other blood lipid concentrations)
- Xanthoma measurement (with a ruler and X-ray of the foot)
Detailed description
Homozygous sitosterolemia is an autosomally inherited recessive disorder of sterol metabolism. Patients with homozygous sitosterolemia can present with accelerated atherosclerosis with initial CHD events occurring in childhood. In addition, these patients can have tendon xanthomas, hemolytic episodes, as well as arthritis and arthralgias. Plasma levels of sitosterol and other dietary sterols are markedly elevated in homozygous sitosterolemic patients, and are diagnostic of this disorder. A low sterol diet provides only limited reduction in sitosterol levels and currently available medical treatments, such as bile salt binding resins, are usually insufficiently effective or poorly tolerated.
SCH-58235 is a member of a new class of therapeutic agents, specific cholesterol absorption inhibitors, being developed to treat hypercholesterolemia. Preclinical animal studies and clinical studies in humans have demonstrated significant reductions in serum cholesterol levels with SCH-58235 treatment. In the current study, the efficacy and safety of SCH-58235 will be studied in patients with homozygous sitosterolemia, an inherited condition in which a wide range of plant sterols, including sitosterol, are excessively absorbed and inadequately excreted, leading to dramatic increases in tissue deposition. SCH-58235 may lower sitosterol levels by directly inhibiting sitosterol absorption (since plant sterols and cholesterol are structurally similar sterols) and/or by inhibiting cholesterol absorption and indirectly by increasing hepatic uptake of plasma LDL with increased cholesterol and sitosterol excretion. These mechanisms of action could lead to reductions in both plant sterol and LDL cholesterol levels in these patients, thereby providing important clinical benefits. The current study will determine if SCH-58235 will be safe and well tolerated and provide significant reductions in plant sterols (plasma sitosterol and campesterol) and low-density lipoprotein-cholesterol (LDL-C) concentrations in patients with homozygous sitosterolemia.
This is a multicenter, randomized, double-blind, placebo-controlled study lasting 12 weeks. Patients with a diagnosis of homozygous sitosterolemia who have an elevated plasma sitosterol level on their current regimen will be studied. Patients will be eligible to enroll in the study whether their current regimen is medication(s), surgical (prior ileal bypass), apheresis, a combination of treatments, or no active regimen. The primary objective of this study is to evaluate the efficacy and safety of 10 mg/day of SCH-58235 in patients with homozygous sitosterolemia who continue to have an elevated plasma sitosterol level.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (20 listed)
- Male or female, age greater than or equal to 10 years are eligible.
- Patients must have a diagnosis of homozygous sitosterolemia with an elevated plasma sitosterol level (greater than 5 mg/dL at screening visit) on their current regimen.
- All women of childbearing potential must be practicing an effective method of contraception.
- All women of childbearing potential must have a negative urine pregnancy test within 72 hours prior to the start of the study medication.
- Patients must not have any condition which, in the opinion of the investigator, would be likely to render the patient unable to complete the study or for which study participation would produce significant risk or not be in the best interests of the patient.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| SCH-58235 | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 1431587Salen G, Shefer S, Nguyen L, Ness GC, Tint GS, Shore V. Sitosterolemia. J Lipid Res. 1992 Jul;33(7):945-55.
- Background: PubMed 1911714Bhattacharyya AK, Connor WE, Lin DS, McMurry MM, Shulman RS. Sluggish sitosterol turnover and hepatic failure to excrete sitosterol into bile cause expansion of body pool of sitosterol in patients with sitosterolemia and xanthomatosis. Arterioscler Thromb. 1991 Sep-Oct;11(5):1287-94. doi: 10.1161/01.atv.11.5.1287.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 SCH-58235 in people with Lipoidosis, 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 20 inclusion and 0 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 4 Mar 2008. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00045812, which also lists 2 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 4 Mar 2008.