AtherosclerosisPhase 1NCT03014830
Alirocumab and Reverse Cholesterol Transport
A Phase 1 study testing Alirocumab in people with Atherosclerosis and Coronary Heart Disease, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Alirocumab is an injectable treatment for elevated blood cholesterol. The hypothesis of this study is that it also increases cholesterol excretion from the body into the stool, a process sometimes called reverse cholesterol transport. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Atherosclerosis, Coronary Heart Disease
- What is being tested?
- Alirocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2017to 30 Jul 2018
- Phase
- Phase 1
- 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 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy or with stable medical or surgical illnesses
- LDL>100 mg/dl.
Who cannot join
- Triglycerides>250
- Taking drugs affecting lipid metabolism
- Elevated liver function tests
- Diabetes mellitus
- A1c 6.5% or greater
- Pregnant
- Breastfeeding
- Desire for conception in either sex.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Effect of Alirocumab on Reverse Cholesterol Transport in Humans
Alirocumab is an injectable treatment for elevated blood cholesterol. The hypothesis of this study is that it also increases cholesterol excretion from the body into the stool, a process sometimes called reverse cholesterol transport. A cholesterol metabolic study will be done before and after 6 weeks of alirocumab treatment. If alirocumab increases reverse cholesterol transport, it is possible that this action provides additional protection from cardiovascular disease.
Read the detailed description
This study is a single-site, randomized, placebo-controlled clinical trial in which about 24 subjects are expected to complete an 8-week study period. The performance site is Washington University School of Medicine. Even though alirocumab is an approved drug, the investigators consider this to be a phase I trial because it is a physiological study in which the primary endpoint is change in fecal cholesterol excretion and measures of reverse cholesterol transport. It is not a treatment protocol and uses healthy subjects.
Subjects with greater than ideal cholesterol but not taking cholesterol lowering drugs will be studied. All receive whole body cholesterol metabolism tests before and after treatment for 6 weeks with either alirocumab or placebo. Each test takes 2 weeks. On the first day the subjects receive about 35 mg cholesterol-d7 intravenously and blood samples are obtained in order to measure cholesterol turnover rate, pool size, esterification rate, transfer from HDL to LDL and removal from the plasma compartment. Fecal cholesterol excretion and related parameters are measured on days 13 and 14 after a relative steady-state is obtained. During this time the subjects consume a metabolic kitchen diet controlled in cholesterol and phytosterol content and consume oral tracer capsules consisting of cholesterol-d5 and sitostanol-d4. Plasma and stool samples are analyzed by gas chromatography/tandem mass spectrometry to determine daily percent cholesterol excretion from rapidly-mixing body cholesterol pools, fecal cholesterol mass and percent cholesterol absorption. The cholesterol metabolic test is repeated on day 43 and final measurements are made on day 57. Treatment effect, defined as the difference between active and placebo treatments is then calculated. Based on animal data it is expected that alirocumab will increase the efficiency of cholesterol excretion from body pools and the rate of removal of cholesterol ester from plasma.
- Conditions
- Atherosclerosis, Coronary Heart Disease
- Being tested
- Alirocumab, Placebos
- Medical subject headings
- Atherosclerosis, Coronary Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlirocumabDrug
Also called Praluent
150 mg SQ every 2 weeks
PlacebosDrug
Also called Placebo
Placebo injections SQ every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Alirocumab | Active comparator | Subjects will receive alirocumab for 6 weeks. Receives: Drug: Alirocumab |
| Placebos | Placebo comparator | Subjects will receive placebo for 6 weeks. Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in percent cholesterol excretion per day.
Percent cholesterol excretion per day is defined as the percent of endogenous rapidly-mixing cholesterol pools excreted per day into the stool.
Measured: Measurements made on days 13-15 (baseline) and days 55-57 (on treatment).
Change from baseline in removal rate of esterified cholesterol from plasma per day.
The removal rate of esterified cholesterol from plasma per day is defined as fractional removal rate of esterified cholesterol from the plasma in pools/day.
Measured: Measurements made on days 1-3 (baseline) and days 43-45 (on treatment).
Secondary outcomes (2)
Change from baseline in LDL cholesterol
Reduction in LDL with alirocumab treatment.
Measured: Measurements made on day 15 (baseline) and day 57 (on treatment).
Change from baseline in percent cholesterol absorption
Percent cholesterol absorption is defined as the percent of intestinal cholesterol absorbed into the body.
Measured: Measurements made on days 13-15 (baseline) and days 55-57 (on treatment).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2017 (estimated)
- Study start1 Jun 2017
- Primary completion4 Jun 2018
- Study completion30 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard E Ostlund, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03014830
- Sponsor's protocol ID
- 201612021
- Status last verified
- Nov 2018
- First submitted
- 6 Dec 2016
- Last updated
- 7 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No plans to share individual data.
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Alirocumab on Reverse Cholesterol Transport in Humans
- ClinicalTrials.gov ID
- NCT03014830
- Acronym / sponsor ID
- 201612021
- Conditions
- Atherosclerosis, Coronary Heart Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 4 Jun 2018 (actual)
- Study completion
- 30 Jul 2018 (actual)
- First posted
- 9 Jan 2017 (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.
Alirocumab is an injectable treatment for elevated blood cholesterol. The hypothesis of this study is that it also increases cholesterol excretion from the body into the stool, a process sometimes called reverse cholesterol transport. A cholesterol metabolic study will be done before and after 6 weeks of alirocumab treatment. If alirocumab increases reverse cholesterol transport, it is possible that this action provides additional protection from cardiovascular disease.
Detailed description
This study is a single-site, randomized, placebo-controlled clinical trial in which about 24 subjects are expected to complete an 8-week study period. The performance site is Washington University School of Medicine. Even though alirocumab is an approved drug, the investigators consider this to be a phase I trial because it is a physiological study in which the primary endpoint is change in fecal cholesterol excretion and measures of reverse cholesterol transport. It is not a treatment protocol and uses healthy subjects.
Subjects with greater than ideal cholesterol but not taking cholesterol lowering drugs will be studied. All receive whole body cholesterol metabolism tests before and after treatment for 6 weeks with either alirocumab or placebo. Each test takes 2 weeks. On the first day the subjects receive about 35 mg cholesterol-d7 intravenously and blood samples are obtained in order to measure cholesterol turnover rate, pool size, esterification rate, transfer from HDL to LDL and removal from the plasma compartment. Fecal cholesterol excretion and related parameters are measured on days 13 and 14 after a relative steady-state is obtained. During this time the subjects consume a metabolic kitchen diet controlled in cholesterol and phytosterol content and consume oral tracer capsules consisting of cholesterol-d5 and sitostanol-d4. Plasma and stool samples are analyzed by gas chromatography/tandem mass spectrometry to determine daily percent cholesterol excretion from rapidly-mixing body cholesterol pools, fecal cholesterol mass and percent cholesterol absorption. The cholesterol metabolic test is repeated on day 43 and final measurements are made on day 57. Treatment effect, defined as the difference between active and placebo treatments is then calculated. Based on animal data it is expected that alirocumab will increase the efficiency of cholesterol excretion from body pools and the rate of removal of cholesterol ester from plasma.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alirocumab | Active comparator | Drug: AlirocumabSubjects will receive alirocumab for 6 weeks. |
| Placebos | Placebo comparator | Drug: PlacebosSubjects will receive placebo for 6 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy or with stable medical or surgical illnesses
- LDL>100 mg/dl.
Key exclusion criteria (8 listed)
- Triglycerides>250
- Taking drugs affecting lipid metabolism
- Elevated liver function tests
- Diabetes mellitus
- A1c 6.5% or greater
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 |
|---|---|---|
| AlirocumabAlso: Praluent150 mg SQ every 2 weeks | Drug | Alirocumab |
| PlacebosAlso: PlaceboPlacebo injections SQ every 2 weeks | Drug | Placebos |
Primary outcome
Change from baseline in percent cholesterol excretion per day.
Time frame: Measurements made on days 13-15 (baseline) and days 55-57 (on treatment).
Percent cholesterol excretion per day is defined as the percent of endogenous rapidly-mixing cholesterol pools excreted per day into the stool.
Change from baseline in removal rate of esterified cholesterol from plasma per day.
Time frame: Measurements made on days 1-3 (baseline) and days 43-45 (on treatment).
The removal rate of esterified cholesterol from plasma per day is defined as fractional removal rate of esterified cholesterol from the plasma in pools/day.
2 secondary outcomes
Change from baseline in LDL cholesterol
Time frame: Measurements made on day 15 (baseline) and day 57 (on treatment).
Change from baseline in percent cholesterol absorption
Time frame: Measurements made on days 13-15 (baseline) and days 55-57 (on treatment).
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 7 Nov 2018.
- Individual participant dataSharing planned: No. No plans to share individual data.
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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.
Richard E Ostlund, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Alirocumab in people with Atherosclerosis and Coronary Heart Disease, run by Washington University School of Medicine 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 8 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 7 Nov 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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.
What does the primary outcome measure?
Change from baseline in percent cholesterol excretion per day. (time frame: Measurements made on days 13-15 (baseline) and days 55-57 (on treatment).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Nov 2018.