Drug IntolerancePhase 4ImmunoStatNCT02984293
Statin Immune Study
A Phase 4 study testing Atorvastatin in people with Drug Intolerance, run by University of Dundee at 1 site in United Kingdom.
Trial summary
Statins are widely used drugs to treat hypercholesterolaemia. In general, they are very safe drugs. However, up to one third of statin users can experience muscle symptoms, which are most commonly mild without any conventional laboratory signs of muscle damage. Read more about this study
- Who is it for?
- Ages 40 to 69 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Intolerance
- What is being tested?
- Atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Apr 2017to 3 Nov 2017
- 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 40 to 69 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 40-69 years
- Statin-naïve
- White European
- Healthy
- Acceptable laboratory test results
Who cannot join
- Significant disease
- Regular drug therapy
- Recent involvement (<30 days) in a CTIMP
- Inability/unwillingness to comply with the protocol
- Carry the rare variant of the CKM polymorphism rs11559024
- Unable to consent
- Woman of childbearing potential (i.e. premenopausal female capable of becoming pregnant)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of LILRB5 Genotype on Immune Response to Atorvastatin
Statins are widely used drugs to treat hypercholesterolaemia. In general, they are very safe drugs. However, up to one third of statin users can experience muscle symptoms, which are most commonly mild without any conventional laboratory signs of muscle damage. However, these muscle symptoms can often lead to poor compliance to the cholesterol-lowering therapy, reducing its effectiveness. Recent data has highlighted the potential role of immune system in development of statin-induced muscle pain. Variation in the LILRB5 gene has been associated with statin intolerance. We aim to investigate the impact of LILRB5 genetic variability in tolerability and immune response to atorvastatin in healthy volunteers.
The study is being undertaken at the Tayside Institute for Cardiovascular Research (TICR) in Ninewells Hospital, Dundee. We will recruit participants who have donated a sample to GoSHARE study. The participants will be healthy, and recruited according to their genotype of LILRB5 (information available from GoSHARE). The volunteers will then enter a randomised cross-over study with two treatment periods. During treatment period one, all participants will be commenced on atorvastatin or placebo (a dummy drug). Before and at the end of the treatment period, blood and urine samples will be taken and a muscle symptoms questionnaire will be completed to assess the tolerability and immune response to the study drug exposure. After four weeks, the study drug is stopped for a washout period of three weeks before cross-over commences. Thereafter, during treatment period two, the alternate study drug will be started, and tolerability will be assessed similar to that in period one. The study will last approximately 11 weeks. The volunteers have a total of 5 visits to the TICR.
- Conditions
- Drug Intolerance
- Being tested
- Atorvastatin, Placebo
- Keywords
- Atorvastatin, LILRB5, Statin intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
Atorvastatin 80 mg once daily for 28 days.
PlaceboDrug
Placebo once daily for 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Atorvastatin | Active comparator | The participants will receive atorvastatin (80 mg) orally once daily for 28 days. Receives: Drug: Atorvastatin |
| Placebo | Placebo comparator | The participants will receive matched placebo orally once daily for 28 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome will be the change in CK levels at the end of the treatment from baseline in both treatment periods.
Measured: Measured at baseline (day 0) and day 29 of both treatment periods.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2016 (estimated)
- Study start17 Apr 2017
- Primary completion3 Nov 2017
- Study completion3 Nov 2017
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 Drug IntoleranceStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Tayside
- Responsible party
- Sponsor
- Investigators
- Colin NA Palmer, PhD FSB FRSE, Study chair, University of Dundee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02984293
- Sponsor's protocol ID
- 2016CV05
- Other IDs
- 16/ES/0128
- Acronym
- ImmunoStat
- Status last verified
- Mar 2018
- First submitted
- 2 Dec 2016
- Last updated
- 3 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: As per GoSHARE tissue bank protocol, the data derived from the existing samples will be returned to the tissue bank for research use.
Publications
Dube MP, Zetler R, Barhdadi A, Brown AM, Mongrain I, Normand V, Laplante N, Asselin G, Zada YF, Provost S, Bergeron J, Kouz S, Dufour R, Diaz A, de Denus S, Turgeon J, Rheaume E, Phillips MS, Tardif JC. CKM and LILRB5 are associated with serum levels of creatine kinase. Circ Cardiovasc Genet. 2014 Dec;7(6):880-6. doi: 10.1161/CIRCGENETICS.113.000395. Epub 2014 Sep 11.
PubMed 25214527Alfirevic A, Neely D, Armitage J, Chinoy H, Cooper RG, Laaksonen R, Carr DF, Bloch KM, Fahy J, Hanson A, Yue QY, Wadelius M, Maitland-van Der Zee AH, Voora D, Psaty BM, Palmer CN, Pirmohamed M. Phenotype standardization for statin-induced myotoxicity. Clin Pharmacol Ther. 2014 Oct;96(4):470-6. doi: 10.1038/clpt.2014.121. Epub 2014 Jun 4.
PubMed 24897241
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of LILRB5 Genotype on Immune Response to Atorvastatin
- ClinicalTrials.gov ID
- NCT02984293
- Acronym / sponsor ID
- ImmunoStat / 2016CV05
- Conditions
- Drug Intolerance
- Keywords
- Atorvastatin, LILRB5, Statin intolerance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Collaborators
- NHS Tayside
- Study start
- 17 Apr 2017 (actual)
- Primary completion
- 3 Nov 2017 (actual)
- Study completion
- 3 Nov 2017 (actual)
- First posted
- 6 Dec 2016 (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.
Statins are widely used drugs to treat hypercholesterolaemia. In general, they are very safe drugs. However, up to one third of statin users can experience muscle symptoms, which are most commonly mild without any conventional laboratory signs of muscle damage. However, these muscle symptoms can often lead to poor compliance to the cholesterol-lowering therapy, reducing its effectiveness. Recent data has highlighted the potential role of immune system in development of statin-induced muscle pain. Variation in the LILRB5 gene has been associated with statin intolerance. We aim to investigate the impact of LILRB5 genetic variability in tolerability and immune response to atorvastatin in healthy volunteers.
The study is being undertaken at the Tayside Institute for Cardiovascular Research (TICR) in Ninewells Hospital, Dundee. We will recruit participants who have donated a sample to GoSHARE study. The participants will be healthy, and recruited according to their genotype of LILRB5 (information available from GoSHARE). The volunteers will then enter a randomised cross-over study with two treatment periods. During treatment period one, all participants will be commenced on atorvastatin or placebo (a dummy drug). Before and at the end of the treatment period, blood and urine samples will be taken and a muscle symptoms questionnaire will be completed to assess the tolerability and immune response to the study drug exposure. After four weeks, the study drug is stopped for a washout period of three weeks before cross-over commences. Thereafter, during treatment period two, the alternate study drug will be started, and tolerability will be assessed similar to that in period one. The study will last approximately 11 weeks. The volunteers have a total of 5 visits to the TICR.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atorvastatin | Active comparator | Drug: AtorvastatinThe participants will receive atorvastatin (80 mg) orally once daily for 28 days. |
| Placebo | Placebo comparator | Drug: PlaceboThe participants will receive matched placebo orally once daily for 28 days. |
Who may qualify
- Ages
- 40 to 69 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 40-69 years
- Statin-naïve
- White European
- Healthy
- Acceptable laboratory test results
Key exclusion criteria (7 listed)
- Significant disease
- Regular drug therapy
- Recent involvement (<30 days) in a CTIMP
- Inability/unwillingness to comply with the protocol
- Carry the rare variant of the CKM polymorphism rs11559024
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 |
|---|---|---|
| AtorvastatinAtorvastatin 80 mg once daily for 28 days. | Drug | Atorvastatin |
| PlaceboPlacebo once daily for 28 days. | Drug | Placebo |
Primary outcome
The primary outcome will be the change in CK levels at the end of the treatment from baseline in both treatment periods.
Time frame: Measured at baseline (day 0) and day 29 of both treatment periods.
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 3 Dec 2018.
- Background: PubMed 25214527Dube MP, Zetler R, Barhdadi A, Brown AM, Mongrain I, Normand V, Laplante N, Asselin G, Zada YF, Provost S, Bergeron J, Kouz S, Dufour R, Diaz A, de Denus S, Turgeon J, Rheaume E, Phillips MS, Tardif JC. CKM and LILRB5 are associated with serum levels of creatine kinase. Circ Cardiovasc Genet. 2014 Dec;7(6):880-6. doi: 10.1161/CIRCGENETICS.113.000395. Epub 2014 Sep 11.
- Background: PubMed 24897241Alfirevic A, Neely D, Armitage J, Chinoy H, Cooper RG, Laaksonen R, Carr DF, Bloch KM, Fahy J, Hanson A, Yue QY, Wadelius M, Maitland-van Der Zee AH, Voora D, Psaty BM, Palmer CN, Pirmohamed M. Phenotype standardization for statin-induced myotoxicity. Clin Pharmacol Ther. 2014 Oct;96(4):470-6. doi: 10.1038/clpt.2014.121. Epub 2014 Jun 4.
- Individual participant dataSharing planned: Yes. As per GoSHARE tissue bank protocol, the data derived from the existing samples will be returned to the tissue bank for research use.
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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.
Colin NA Palmer, PhD FSB FRSE study chair
University of Dundee
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 Atorvastatin in people with Drug Intolerance, run by University of Dundee 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 5 inclusion and 7 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 3 Dec 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 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. 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 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?
The primary outcome will be the change in CK levels at the end of the treatment from baseline in both treatment periods. (time frame: Measured at baseline (day 0) and day 29 of both treatment periods.). 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 NCT02984293, 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 3 Dec 2018.