HypercholesterolemiaPhase 4NCT01054508
Effect of Tredaptive on Serum Lipoproteins and Inflammatory Markers
A Phase 4 study testing nicotinic acid/laropiprant in people with Hypercholesterolemia, run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Cardiovascular disease (CVD) is associated with high levels of low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol. CVD results from 'hardening of the arteries' when there is a build-up of cholesterol in the walls of blood vessels. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- nicotinic acid/laropiprant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2010to Jan 2012
- Phase
- Phase 4
- 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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -Men and women who are taking cholesterol-lowering medication (maximum tolerated statins and/or ezetimibe) and who have not reached the recommended LDL target of less than 1.8 mmol/l (70 mg/l). Ezetimibe will be stopped 4 weeks before entering the study.
Who cannot join
- Pregnant and/or breast-feeding women.
- Significant renal impairment (eGFR < 59ml/min).
- Active liver disease and transaminases > 3 times upper limit of normal range.
- Patients on fibrates.
- Patients on Omacor.
- Patients who are allergic to nicotinic acid.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Tredaptive on Serum Lipoproteins, Lipoproteins Metabolism, Oxidative Stress and HDL Antioxidant Function
Cardiovascular disease (CVD) is associated with high levels of low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol.
CVD results from 'hardening of the arteries' when there is a build-up of cholesterol in the walls of blood vessels. LDL is the main carrier of cholesterol in the body. LDL particles are responsible for transporting cholesterol that is deposited in vessel walls. LDL particles can also be altered in structure and turn into an irritant to the vessel walls. The body responds to the irritating effect of LDL by producing substances that result in inflammation. This sequence of events eventually leads to the vessels becoming permanently damaged. HDL has a protective role in CVD. It is associated with the enzyme paraoxonase which protects the body from the damaging effects of altered LDL particles.
Read more
Nicotinic acid (niacin) has the ability to lower LDL levels and raise HDL levels thus reducing the incidence of CVD. Our study aims to show that niacin not only has good effects on cholesterol levels but is also able to reduce inflammation. Niacin is often poorly tolerated due to flushing side effect. Tredaptive is a formulation that combines niacin with laropiprant, an agent that reduces flushing hence improving tolerability and compliance.
Patients who are receiving cholesterol-lowering medication and whose LDL levels have not reached the recommended target are recruited to the study. The study will be conducted at the Manchester Royal Infirmary. The study has two consecutive 16 week periods. In each period patients will be randomised to either tredaptive or placebo. They will attend for 5 monitoring visits. Apart from the first visit, fasting blood samples will be taken from them during all subsequent visits.
Read the detailed description
The design is a placebo-controlled cross-over study. The study has 2 consecutive 16 week periods. If a patient satisfies the inclusion/exclusion criteria and consents to participate in the study, he/she will enter a 4-week placebo run-in period. This is followed by a 12-week treatment period where the patient will be assigned tredaptive or placebo randomly. At the end of the treatment period the patient will enter a second 4-week placebo period before going onto the second 12-week treatment period. Patients who are randomised to placebo in the first treatment period will receive tredaptive in the second treatment period and vice versa. Thus all participating patients will receive active medication for one treatment period in the study.
Patients will continue taking statins for the duration of the study, ensuring the cholesterol-lowering benefits they have from their usual medication are not compromised.
Patients will be recruited from the Lipid Clinic at the Manchester Royal Infirmary. The study will be explained fully to the patients who will have time to ask questions. Information leaflets will be given to patients who will be encouraged to take at least 1 day to discuss the study with their families, friends and general practitioners before consenting.
The study comprises 5 visits. At the first visit, informed consent will be taken from the patients. The visit also includes history taking and physical examination. Subsequent visits take place at the end of 4th and 16th weeks. This is repeated for the second 16 week period. Apart from the first visit, patients will be required to give a blood sample of 50 ml at each of the visits. They will be asked to fast overnight (from 22.00 hours) the day before the visit and blood sampling will be done before midday the following day. Blood will be taken by an experienced doctor or nurse and the only risks involved may be bruising at the puncture site.
- Conditions
- Hypercholesterolemia
- Being tested
- nicotinic acid/laropiprant
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nicotinic acid/laropiprantDrug
Also called Tredaptive
Nicotinic acid/laropiprant (1g/20mg) daily for 4 weeks, then nicotinic acid/laropiprant (2g/40mg) daily for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Placebo (4 weeks) --> Placebo (12 weeks) --> Placebo (4 weeks) --> Tredaptive (12 weeks) | Other | Placebo (4 weeks) --> Placebo (12 weeks) --> Placebo (4 weeks) --> Tredaptive (12 weeks) There were two interventional periods of 12 weeks during which patients received either Placebo or Tredaptive (nicotinic acid/laropiprant). Patient who received Tredaptive were given dosages of 1g/20mg for 4 weeks followed by 2g/40mg for 8 weeks. Receives: Drug: nicotinic acid/laropiprant |
| Arm 2: Placebo (4 weeks) --> Tredaptive (12 weeks) --> Placebo (4 weeks) --> Placebo (12 weeks) | Other | Placebo (4 weeks) --> Tredaptive (12 weeks) --> Placebo (4 weeks) --> Placebo (12 weeks) There were two interventional periods of 12 weeks during which patients received either Placebo or Tredaptive (nicotinic acid/laropiprant). Patient who received Tredaptive were given dosages of 1g/20mg for 4 weeks followed by 2g/40mg for 8 weeks. Receives: Drug: nicotinic acid/laropiprant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in HDL Levels
As exactly listed in the protocol, the primary outcome will be changes in HDL-C level. The mean value will be assessed before and after treatment. This level will be compared to the mean value between the placebo and Tredaptive groups.
Measured: 14 months
Secondary outcomes (3)
Changes in paraoxonase activity
Changes in PON1
Measured: 14 months
Changes in LDL
Changes in oxidised LDL and glycated LDL
Measured: 14 months
Changes in HDL inflammatory index
Changes in HDL inflammatory index
Measured: 14 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2010 (estimated)
- Study startJun 2010
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Manchester University NHS Foundation Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Handrean Soran, MRCP, Principal investigator, Manchester University NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01054508
- Sponsor's protocol ID
- TRED012010
- Other IDs
- R01049
- Status last verified
- Oct 2020
- First submitted
- 21 Jan 2010
- Last updated
- 29 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Yadav R, Liu Y, Kwok S, Hama S, France M, Eatough R, Pemberton P, Schofield J, Siahmansur TJ, Malik R, Ammori BA, Issa B, Younis N, Donn R, Stevens A, Durrington P, Soran H. Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients. J Am Heart Assoc. 2015 Sep 15;4(9):e001508. doi: 10.1161/JAHA.114.001508.
PubMed 26374297
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Tredaptive on Serum Lipoproteins, Lipoproteins Metabolism, Oxidative Stress and HDL Antioxidant Function
- ClinicalTrials.gov ID
- NCT01054508
- Acronym / sponsor ID
- TRED012010
- Conditions
- Hypercholesterolemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Manchester University NHS Foundation TrustOther government
- Study start
- Jun 2010
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 22 Jan 2010 (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.
Cardiovascular disease (CVD) is associated with high levels of low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol.
CVD results from 'hardening of the arteries' when there is a build-up of cholesterol in the walls of blood vessels. LDL is the main carrier of cholesterol in the body. LDL particles are responsible for transporting cholesterol that is deposited in vessel walls. LDL particles can also be altered in structure and turn into an irritant to the vessel walls. The body responds to the irritating effect of LDL by producing substances that result in inflammation. This sequence of events eventually leads to the vessels becoming permanently damaged. HDL has a protective role in CVD. It is associated with the enzyme paraoxonase which protects the body from the damaging effects of altered LDL particles.
Nicotinic acid (niacin) has the ability to lower LDL levels and raise HDL levels thus reducing the incidence of CVD. Our study aims to show that niacin not only has good effects on cholesterol levels but is also able to reduce inflammation. Niacin is often poorly tolerated due to flushing side effect. Tredaptive is a formulation that combines niacin with laropiprant, an agent that reduces flushing hence improving tolerability and compliance.
Patients who are receiving cholesterol-lowering medication and whose LDL levels have not reached the recommended target are recruited to the study. The study will be conducted at the Manchester Royal Infirmary. The study has two consecutive 16 week periods. In each period patients will be randomised to either tredaptive or placebo. They will attend for 5 monitoring visits. Apart from the first visit, fasting blood samples will be taken from them during all subsequent visits.
Detailed description
The design is a placebo-controlled cross-over study. The study has 2 consecutive 16 week periods. If a patient satisfies the inclusion/exclusion criteria and consents to participate in the study, he/she will enter a 4-week placebo run-in period. This is followed by a 12-week treatment period where the patient will be assigned tredaptive or placebo randomly. At the end of the treatment period the patient will enter a second 4-week placebo period before going onto the second 12-week treatment period. Patients who are randomised to placebo in the first treatment period will receive tredaptive in the second treatment period and vice versa. Thus all participating patients will receive active medication for one treatment period in the study.
Patients will continue taking statins for the duration of the study, ensuring the cholesterol-lowering benefits they have from their usual medication are not compromised.
Patients will be recruited from the Lipid Clinic at the Manchester Royal Infirmary. The study will be explained fully to the patients who will have time to ask questions. Information leaflets will be given to patients who will be encouraged to take at least 1 day to discuss the study with their families, friends and general practitioners before consenting.
The study comprises 5 visits. At the first visit, informed consent will be taken from the patients. The visit also includes history taking and physical examination. Subsequent visits take place at the end of 4th and 16th weeks. This is repeated for the second 16 week period. Apart from the first visit, patients will be required to give a blood sample of 50 ml at each of the visits. They will be asked to fast overnight (from 22.00 hours) the day before the visit and blood sampling will be done before midday the following day. Blood will be taken by an experienced doctor or nurse and the only risks involved may be bruising at the puncture site.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Placebo (4 weeks) --> Placebo (12 weeks) --> Placebo (4 weeks) --> Tredaptive (12 weeks) | Other | Drug: nicotinic acid/laropiprantPlacebo (4 weeks) --> Placebo (12 weeks) --> Placebo (4 weeks) --> Tredaptive (12 weeks) There were two interventional periods of 12 weeks during which patients received either Placebo or Tredaptive (nicotinic acid/laropiprant). Patient who received Tredaptive were given dosages of 1g/20mg for 4 weeks followed by 2g/40mg for 8 weeks. |
| Arm 2: Placebo (4 weeks) --> Tredaptive (12 weeks) --> Placebo (4 weeks) --> Placebo (12 weeks) | Other | Drug: nicotinic acid/laropiprantPlacebo (4 weeks) --> Tredaptive (12 weeks) --> Placebo (4 weeks) --> Placebo (12 weeks) There were two interventional periods of 12 weeks during which patients received either Placebo or Tredaptive (nicotinic acid/laropiprant). Patient who received Tredaptive were given dosages of 1g/20mg for 4 weeks followed by 2g/40mg for 8 weeks. |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- -Men and women who are taking cholesterol-lowering medication (maximum tolerated statins and/or ezetimibe) and who have not reached the recommended LDL target of less than 1.8 mmol/l (70 mg/l). Ezetimibe will be stopped 4 weeks before entering the study.
Key exclusion criteria (6 listed)
- Pregnant and/or breast-feeding women.
- Significant renal impairment (eGFR < 59ml/min).
- Active liver disease and transaminases > 3 times upper limit of normal range.
- Patients on fibrates.
- Patients on Omacor.
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 |
|---|---|---|
| nicotinic acid/laropiprantAlso: TredaptiveNicotinic acid/laropiprant (1g/20mg) daily for 4 weeks, then nicotinic acid/laropiprant (2g/40mg) daily for 8 weeks. | Drug | Arm 1: Placebo (4 weeks) --> Placebo (12 weeks) --> Placebo (4 weeks) --> Tredaptive (12 weeks), Arm 2: Placebo (4 weeks) --> Tredaptive (12 weeks) --> Placebo (4 weeks) --> Placebo (12 weeks) |
Primary outcome
Changes in HDL Levels
Time frame: 14 months
As exactly listed in the protocol, the primary outcome will be changes in HDL-C level. The mean value will be assessed before and after treatment. This level will be compared to the mean value between the placebo and Tredaptive groups.
3 secondary outcomes
Changes in paraoxonase activity
Time frame: 14 months
Changes in LDL
Time frame: 14 months
Changes in HDL inflammatory index
Time frame: 14 months
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 29 Oct 2020.
- Derived from this study: PubMed 26374297Yadav R, Liu Y, Kwok S, Hama S, France M, Eatough R, Pemberton P, Schofield J, Siahmansur TJ, Malik R, Ammori BA, Issa B, Younis N, Donn R, Stevens A, Durrington P, Soran H. Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients. J Am Heart Assoc. 2015 Sep 15;4(9):e001508. doi: 10.1161/JAHA.114.001508.
Related trials for Hypercholesterolemia
Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia
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.
Handrean Soran, MRCP principal investigator
Manchester University NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing nicotinic acid/laropiprant in people with Hypercholesterolemia, run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
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 1 inclusion and 6 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 29 Oct 2020. 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 Kingdom. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Changes in HDL Levels (time frame: 14 months). 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 NCT01054508, which also lists 1 linked publication.
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 29 Oct 2020.