Self-Assessment Method for Statin Side-effects Or Nocebo

NCT02668016 | Completed Phase 4 Results DMC

• 2 other identifiers: 15SM29472015-004109-18
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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 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.

1. 1.Hypothesis 1: that \>30% of participants enrolling for the study will complete it.
2. 2.Hypothesis 2: Overall \>50% of symptom burden is nocebo rather than pharmacological
3. 3.The investigators will define the Nocebo proportion of side effects.
4. 4.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.

Conditions

Adverse Effects; Cardiovascular Diseases; Hyperlipidemias

Keywords

cardiovascular diseases; hyperlipidemias

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (2)

• Number of Participants Currently Being Prescribed Statins

  At 6-months after the end of trial up to 7-months

• Attribution of Adverse Symptoms

  6-months after end of trial

Study Arms (3)

Atorvastatin 20mg Daily

EXPERIMENTAL

Atorvastatin 20mg daily for 1 month

Drug: Atorvastatin

Placebo

PLACEBO COMPARATOR

Placebo daily for 1 month

Other: Placebo

No Treatment

NO INTERVENTION

No Atorvastatin or placebo for 1 month

Interventions

Atorvastatin DRUG

Atorvastatin 20mg tablets taken orally once daily for one month.

Also known as: HMG CoA reductase inhibitors, Statins

Atorvastatin 20mg Daily

Placebo OTHER

Placebo tablets taken orally once daily for one month

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College London

London, Greater London, W12 0HS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34531021 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Hyperlipidemias

Interventions

Atorvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Limitations and Caveats

To be eligible for the trail, patients' previous perceived side effects whilst taking statins must have arisen within 2 weeks of commencing the drug. This is to ensure the 1 month long blocks are long enough that symptoms would be expected to arise. Patients whose symptoms take longer than 2 weeks to arise were not eligible for this study.

Results Point of Contact

• Title: Professor Darrel Francis
• Organization: Imperial College London

d.francis@imperial.ac.uk

0207 594 9647

Study Officials

• Darrel P Francis, MB MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2016
• First Posted: January 29, 2016
• Study Start: March 1, 2016
• Primary Completion: October 31, 2020
• Study Completion: December 31, 2020
• Last Updated: August 7, 2024
• Results First Posted: August 7, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)