Adverse EffectsPhase 4SAMSONNCT02668016
Self-Assessment Method for Statin Side-effects Or Nocebo
A Phase 4 study testing Atorvastatin in people with Adverse Effects and Cardiovascular Diseases, run by Imperial College London at 1 site in United Kingdom.
Trial summary
Front-line clinicians cannot currently test for an individual participant whether symptoms experienced are the pharmacological result of a statin or due to other phenomena. In this trial, participants who have previously ceased statins due to side effects will be offered the opportunity to undergo twelve randomly… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adverse Effects, Cardiovascular Diseases, Hyperlipidemias
- 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
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2016to 31 Dec 2020
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 years or older
- Previously taken one or more statins
- Withdrawn from statins because of perceived side effects
- Developed side effects within 2 weeks of initiation
- Clinical indication for statins for primary or secondary prevention of cardiovascular disease or dyslipidaemia, on either no medication or non-statin lipid lowering therapy (e.g, ezetimibe)
Who cannot join
- History of neuropathy
- Regularly taking prescribed analgesia
- History of a chronic pain condition
- History of severe mental illness (as their experience of symptoms may already be altered)
- Current use of fibrates (because of the risk of interaction with statins; will not exclude participants taking ezetimibe).
- Severe previous reaction or reaction considered immunological, such as anaphylaxis, facial swelling, severe rash, muscle ache with rise in serum creatine kinase, inflammatory myopathy, rhabdomyolysis or liver function abnormalities (aspartate transaminase (AST) or alanine transaminase (ALT) greater than 3 times upper limit or normal).
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- Side-effects taking longer than 2 weeks to develop (because in such participants much longer blocks of treatment would be required; if the present study is positive such studies will be planned for the future).
- History of statin intolerance with drug interaction to antiretroviral drugs.
- Currently taking antiretrovirals with known interaction to statins
- Currently taking any drug other than antiretrovirals with known interaction to statins
- Side effects taking longer than 2 weeks to present.
- In clinical judgement of study doctor, participant should not participate.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College London
London, Greater London, W12 0HS
About this study
Front-line clinicians cannot currently test for an individual participant whether symptoms experienced are the pharmacological result of a statin or due to other phenomena. In this trial, participants who have previously ceased statins due to side effects will be offered the opportunity to undergo twelve randomly ordered 1-month periods. There will be four periods of no medication, four periods of placebo and four periods of statin. The placebo and the statin pills will be identical in appearance. Participants will record on a daily basis side-effects experienced. At the end of the study, the one-month sessions are sorted into the order shown above. The participant can then observe directly how much of the increase in symptoms seen with statin is also seen with placebo.
- Hypothesis 1: that >30% of participants enrolling for the study will complete it.
- Hypothesis 2: Overall >50% of symptom burden is nocebo rather than pharmacological
- The investigators will define the Nocebo proportion of side effects.
- Hypothesis 3: that the majority of participants, at 6 months after completion, will either be taking statins or have declined statins for reasons other than perceived side effects.
Read the detailed description
Participants: 50 participants will be recruited to the trial.
Method: At baseline each participant will have a detailed interview with the study doctor to assess past medical history and previous symptoms attributed to statins and assess if they are eligible to be enrolled. Eligible participants will be enrolled and allocated a random predefined order to take the study interventions in. These random codes will be generated by the trials unit statistician and supplied to the production pharmacy. The participant will be dispensed High Density Polyethylene (HDPE) containers which are in this pre-specified order. Each participant will receive 12 sets of HDPE containers pre-labelled. 4 sets of HDPE containers will contain no medication, 4 will contain 1-month supply of matched placebo and 4 will contain 1-month supply of atorvastatin 20mg. At the start of the next calendar month after the screening visit the participants will commence the trial intervention. The research nurse will call the participant to remind them to start on the 1st day of the next month after screening. Each day participants will rate their daily symptom on a phone application and will also complete 3 additional questionnaires on a monthly basis. The study nurse will call the participant at the end of each month to assess their progress in the trial. Each participant will return their boxes at dispensing visits (if applicable) and at the study end in order for a pill count to be undertaken to assess medication adherence. The placebo and atorvastatin pills will be visually identical.
The study enrols participants not intending to re-start clinical use of statins. Participants' other medications will continue to be managed as normal by their own physicians, with no restriction on starting, stopping or changing doses. For safety reasons the participant's own physician will be asked to consult the investigators prior to consideration of starting, or amending the dose of, any other lipid lowering medication.
For the trial, each participant will receive a smartphone, or if preferred, can have the application downloaded to their existing phone to allow real-time daily documentation of symptoms experienced on a visual analogue scale of 0-100. Participants will receive training on the simple touch-screen interface and a leaflet with further information will also be provided. Participants will rate symptoms every day, with the daily scores aggregated into a monthly score. This is preferable over scoring only once a month, because participants may struggle to remember and aggregate their symptom burden especially if it varies between days.
Each month participants will fill out two validated questionnaires on the impact of their side-effects on their quality of life. These are EuroQol (EQ-5D-3L), a well-validated measure of health related quality of life, and the Treatment Satisfaction Questionnaire for Medicine (TSQM) questionnaire, a validated treatment satisfaction questionnaire. EQ-5D-3L assesses five domains of health and overall self-rated health using a visual analogue scale. EQ-5D-3L is conventional for assessing efficacy of medication on quality of life but may not be sufficient for assessing side effects, therefore the TSQM questionnaire will also be used. Use of both a health related quality of life questionnaire and a treatment satisfaction questionnaire will allow assessment of participants' multiple health states, overall self-rated health status and treatment satisfaction, and provide a test of both convergent validity and measurement invariance for the monthly aggregate symptom burden score.
The investigators will also ask participants to fill in a short questionnaire detailing any potentially their own physicians, with no restriction on starting, stopping or changing doses For safety reasons the participant's own physician will be asked to consult the investigators prior to consideration of starting, or amending the dose of, any other lipid lowering medication.
- Conditions
- Adverse Effects, Cardiovascular Diseases, Hyperlipidemias
- Being tested
- Atorvastatin, Placebo
- Keywords
- cardiovascular diseases, hyperlipidemias
- Medical subject headings
- Cardiovascular Diseases, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
Also called HMG CoA reductase inhibitors, Statins
Atorvastatin 20mg tablets taken orally once daily for one month.
PlaceboOther
Placebo tablets taken orally once daily for one month
| Study group | Role | What they receive |
|---|---|---|
| Atorvastatin 20mg Daily | Experimental | Atorvastatin 20mg daily for 1 month Receives: Drug: Atorvastatin |
| Placebo | Placebo comparator | Placebo daily for 1 month Receives: Other: Placebo |
| No Treatment | No intervention | No Atorvastatin or placebo for 1 month |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Symptom Scores Across Statin, Placebo and no Treatment Periods
The full scale name would be "daily symptom score" measuring patient-reported symptoms on a scale from 0 (no symptoms) to 100 (worst imaginable symptoms). The unit of measurement would be "scores on a scale".
The mean symptom scores for the four months on each arm will be calculated: placebo, Atorvastatin 20mg and no treatment. Mean symptom scores across statin, placebo and no treatment periods is calculated. There are no subscales/subranges.
Measured: 12 months
Secondary outcomes (2)
Number of Participants Currently Being Prescribed Statins
Following the end of the trial, is the trial participant taking statins or not.
Measured: At 6-months after the end of trial up to 7-months
Attribution of Adverse Symptoms
Following the end of the trial, whether individual trial participants currently believe that most of the side-effects previously attributed to the statin, were indeed a pharmacological effect of the statin.
Measured: 6-months after end of trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2016 (estimated)
- Study startMar 2016
- Primary completion31 Oct 2020
- Study completion31 Dec 2020
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 (1)Papers the sponsor has linked to this study.
- Other trials for Adverse EffectsStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Darrel P Francis, MB MD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02668016
- Sponsor's protocol ID
- 15SM2947
- Other IDs
- 2015-004109-18, 2015
- Acronym
- SAMSON
- Status last verified
- Aug 2024
- First submitted
- 19 Jan 2016
- Last updated
- 7 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Howard JP, Wood FA, Finegold JA, Nowbar AN, Thompson DM, Arnold AD, Rajkumar CA, Connolly S, Cegla J, Stride C, Sever P, Norton C, Thom SAM, Shun-Shin MJ, Francis DP. Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment. J Am Coll Cardiol. 2021 Sep 21;78(12):1210-1222. doi: 10.1016/j.jacc.2021.07.022.
PubMed 34531021
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Self-Assessment Method for Statin Side-effects Or Nocebo
- ClinicalTrials.gov ID
- NCT02668016
- Acronym / sponsor ID
- SAMSON / 15SM2947
- Conditions
- Adverse Effects, Cardiovascular Diseases, Hyperlipidemias
- Keywords
- cardiovascular diseases, hyperlipidemias
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- 31 Oct 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 29 Jan 2016 (estimated)
- Results
- Posted 7 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Front-line clinicians cannot currently test for an individual participant whether symptoms experienced are the pharmacological result of a statin or due to other phenomena. In this trial, participants who have previously ceased statins due to side effects will be offered the opportunity to undergo twelve randomly ordered 1-month periods. There will be four periods of no medication, four periods of placebo and four periods of statin. The placebo and the statin pills will be identical in appearance. Participants will record on a daily basis side-effects experienced. At the end of the study, the one-month sessions are sorted into the order shown above. The participant can then observe directly how much of the increase in symptoms seen with statin is also seen with placebo.
- Hypothesis 1: that >30% of participants enrolling for the study will complete it.
- Hypothesis 2: Overall >50% of symptom burden is nocebo rather than pharmacological
- The investigators will define the Nocebo proportion of side effects.
- Hypothesis 3: that the majority of participants, at 6 months after completion, will either be taking statins or have declined statins for reasons other than perceived side effects.
Detailed description
Participants: 50 participants will be recruited to the trial.
Method: At baseline each participant will have a detailed interview with the study doctor to assess past medical history and previous symptoms attributed to statins and assess if they are eligible to be enrolled. Eligible participants will be enrolled and allocated a random predefined order to take the study interventions in. These random codes will be generated by the trials unit statistician and supplied to the production pharmacy. The participant will be dispensed High Density Polyethylene (HDPE) containers which are in this pre-specified order. Each participant will receive 12 sets of HDPE containers pre-labelled. 4 sets of HDPE containers will contain no medication, 4 will contain 1-month supply of matched placebo and 4 will contain 1-month supply of atorvastatin 20mg. At the start of the next calendar month after the screening visit the participants will commence the trial intervention. The research nurse will call the participant to remind them to start on the 1st day of the next month after screening. Each day participants will rate their daily symptom on a phone application and will also complete 3 additional questionnaires on a monthly basis. The study nurse will call the participant at the end of each month to assess their progress in the trial. Each participant will return their boxes at dispensing visits (if applicable) and at the study end in order for a pill count to be undertaken to assess medication adherence. The placebo and atorvastatin pills will be visually identical.
The study enrols participants not intending to re-start clinical use of statins. Participants' other medications will continue to be managed as normal by their own physicians, with no restriction on starting, stopping or changing doses. For safety reasons the participant's own physician will be asked to consult the investigators prior to consideration of starting, or amending the dose of, any other lipid lowering medication.
For the trial, each participant will receive a smartphone, or if preferred, can have the application downloaded to their existing phone to allow real-time daily documentation of symptoms experienced on a visual analogue scale of 0-100. Participants will receive training on the simple touch-screen interface and a leaflet with further information will also be provided. Participants will rate symptoms every day, with the daily scores aggregated into a monthly score. This is preferable over scoring only once a month, because participants may struggle to remember and aggregate their symptom burden especially if it varies between days.
Each month participants will fill out two validated questionnaires on the impact of their side-effects on their quality of life. These are EuroQol (EQ-5D-3L), a well-validated measure of health related quality of life, and the Treatment Satisfaction Questionnaire for Medicine (TSQM) questionnaire, a validated treatment satisfaction questionnaire. EQ-5D-3L assesses five domains of health and overall self-rated health using a visual analogue scale. EQ-5D-3L is conventional for assessing efficacy of medication on quality of life but may not be sufficient for assessing side effects, therefore the TSQM questionnaire will also be used. Use of both a health related quality of life questionnaire and a treatment satisfaction questionnaire will allow assessment of participants' multiple health states, overall self-rated health status and treatment satisfaction, and provide a test of both convergent validity and measurement invariance for the monthly aggregate symptom burden score.
The investigators will also ask participants to fill in a short questionnaire detailing any potentially their own physicians, with no restriction on starting, stopping or changing doses For safety reasons the participant's own physician will be asked to consult the investigators prior to consideration of starting, or amending the dose of, any other lipid lowering medication.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Atorvastatin 20mg Daily | Experimental | Drug: AtorvastatinAtorvastatin 20mg daily for 1 month |
| Placebo | Placebo comparator | Other: PlaceboPlacebo daily for 1 month |
| No Treatment | No intervention | –No Atorvastatin or placebo for 1 month |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Aged 18 years or older
- Previously taken one or more statins
- Withdrawn from statins because of perceived side effects
- Developed side effects within 2 weeks of initiation
- Clinical indication for statins for primary or secondary prevention of cardiovascular disease or dyslipidaemia, on either no medication or non-statin lipid lowering therapy (e.g, ezetimibe)
Key exclusion criteria (12 listed)
- History of neuropathy
- Regularly taking prescribed analgesia
- History of a chronic pain condition
- History of severe mental illness (as their experience of symptoms may already be altered)
- Current use of fibrates (because of the risk of interaction with statins; will not exclude participants taking ezetimibe).
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 |
|---|---|---|
| AtorvastatinAlso: HMG CoA reductase inhibitors, StatinsAtorvastatin 20mg tablets taken orally once daily for one month. | Drug | Atorvastatin 20mg Daily |
| PlaceboPlacebo tablets taken orally once daily for one month | Other | Placebo |
Primary outcome
Mean Symptom Scores Across Statin, Placebo and no Treatment Periods
Time frame: 12 months
The full scale name would be "daily symptom score" measuring patient-reported symptoms on a scale from 0 (no symptoms) to 100 (worst imaginable symptoms). The unit of measurement would be "scores on a scale". The mean symptom scores for the four months on each arm will be calculated: placebo, Atorvastatin 20mg and no treatment. Mean symptom scores across statin, placebo and no treatment periods is calculated. There are no subscales/subranges.
2 secondary outcomes
Number of Participants Currently Being Prescribed Statins
Time frame: At 6-months after the end of trial up to 7-months
Attribution of Adverse Symptoms
Time frame: 6-months after end of trial
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34531021Howard JP, Wood FA, Finegold JA, Nowbar AN, Thompson DM, Arnold AD, Rajkumar CA, Connolly S, Cegla J, Stride C, Sever P, Norton C, Thom SAM, Shun-Shin MJ, Francis DP. Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment. J Am Coll Cardiol. 2021 Sep 21;78(12):1210-1222. doi: 10.1016/j.jacc.2021.07.022.
- Individual participant dataSharing planned: No
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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.
Darrel P Francis, MB MD principal investigator
Imperial College London
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 Adverse Effects and Cardiovascular Diseases, run by Imperial College London 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 12 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 Aug 2024. 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?
Yes. Results are posted in the registry (first posted 7 Aug 2024). 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?
Mean Symptom Scores Across Statin, Placebo and no Treatment Periods (time frame: 12 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 NCT02668016, 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 7 Aug 2024.