Neurocognitive Impairment, MildPhase 3STRONGERNCT04904536
Statin TReatment for COVID-19 to Optimise NeuroloGical recovERy
A Phase 3 study testing Atorvastatin in people with Neurocognitive Impairment, Mild, run by The George Institute at 1 site in Australia.
Trial summary
STRONGER is an international, investigator initiated and conducted, pragmatic clinical trial to determine whether 40mg atorvastatin daily can improve neurocognitive function in adults with long COVID neurological symptoms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurocognitive Impairment, Mild
- What is being tested?
- Atorvastatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 190 participants
- Where
- 1 siteAustralia
- Study dates
- 10 Mar 2022to 30 Jul 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Age ≥18 years
- History of COVID-19 that is confirmed by a positive polymerase-chain-reaction (PCR) test,rapid antigen test (RAT) or as per the state guidelines for COVID-19 diagnosis at the time of screening
- Any ongoing neurological symptoms as a result of COVID-19 (e.g. problems with memory, concentration, sleep disturbance and fatigue) that are identified through administration of the checklist of symptoms on the Somatic and Psychological Health Report (SPHERE) questionnaire, or reported loss of smell (anosmia)
- Able to fully participate in all procedures, including cognitive assessments
- Able and willing to provide written informed consent
Who cannot join
- Evidence of dementia and/or significant cognitive impairment on screening (i.e: Blind Montreal Cognitive Assessment [MoCA] score <19/22 in conjunction with clinical assessment)
- Severe co-morbid medical or psychiatric condition that prevents participation
- History of traumatic brain injury with loss of consciousness (>30 mins) within the last 2 years
- Ongoing long-term use for a clear indication (e.g. secondary cardiovascular prevention in high-risk individuals) or any contraindication (e.g. previous adverse reaction) of statin use
- Evidence of severe or significant liver disease, defined as any of the following: acute viral hepatitis; chronic active hepatitis; chronic active hepatitis; cirrhosis; or elevated biochemical function markers i.e. ALT or AST >3x the ULN or eGFR <30mL/min/1.73m2
- Creatine kinase (CK) levels > 2x upper limit of normal (ULN)
Show all 9Show fewer
- Female of child-bearing potential that is unable or unwilling to use reliable method of contraception, breastfeeding, or planning a pregnancy
- For a sub-group of participants undergoing MRI - any contraindication to MRI due to metallic body parts or claustrophobia
- Medical history of a disorder that might, in the opinion of the attending clinician, put the participant at significant risk if they were to participate in the trial
Trial locations and contacts
1 site in 1 country.
Australia1 site
The George Institute for Global Health
Sydney, New South Wales, 2050
About this study
Official title: An International, Investigator Initiated and Conducted, Pragmatic Clinical Trial to Determine Whether 40mg Atorvastatin Daily Can Improve Neurocognitive Function in Adults With Long COVID Neurological Symptoms
STRONGER is an international, investigator initiated and conducted, pragmatic clinical trial to determine whether 40mg atorvastatin daily can improve neurocognitive function in adults with long COVID neurological symptoms. The objective is to determine effectiveness of treatment with 40mg atorvastatin over 12 months on attenuating cognitive decline and neuroinflammatory biomarkers in adults with long COVID neurological symptoms. The study design is a prospective, randomised, open-label, blinded endpoint (PROBE) study of atorvastatin 40mg on top of standard care, in patients with long COVID neurological symptoms.
Read the detailed description
Question: Does treatment with 40mg atorvastatin over 12 months attenuate cognitive decline and neuroinflammatory biomarkers in adults with long COVID neurological symptoms? Aims: In 410 adults who report ongoing alteration of their memory, thinking, concentration or mood after COVID-19 diagnosis, this pragmatic clinical trial aims to determine the effects of standard-dose atorvastatin on improving neurological outcomes with sensitive measures of cognitive function and brain MRI.
Outcome measures include; Primary - processing speed, assessed on the oral Symbol Digit Modalities Test (SDMT). Key Secondary - white matter free water measured on diffusion MRI brain imaging. Other - other components of cognitive function; other health assessments; other MRI markers of cerebral white matter integrity, iron load, cerebral perfusion, and glutathione for oxidative stress; cost-effectiveness compared to standard care. The study sites are established at centralised research clinics located at: The Brain and Mind Centre of the University of Sydney; Alfred Medical Centre linked to Monash University, a research clinic associated with Clínica Alemana Universidad del Desarrollo, Santiago, Chile, and a research clinic associated with The Chinese University of Hong Kong. Additional sites may be set up as required.
- Conditions
- Neurocognitive Impairment, Mild
- Being tested
- Atorvastatin, Standard Care
- Keywords
- clinical trial, COVID-19, neurological symptoms, atorvastatin
- Medical subject headings
- Lymphoma, Follicular, COVID-19, Neurologic Manifestations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
40mg atorvastatin + standard care daily for 12 months.Atorvastatin 40mg has TGA approval for general marketing for the treatment of hypercholesterolaemia and cardiovascular prevention under a number of manufacturer names.The study medication selected will be the atorvastatin 40mg (Apotex) which is scored, and allows down-titration to 20mg should a participant develop symptoms.The study medication will be packaged, labelled and dispensed directly to particpants by the Syntro Health pharmacy in Australia. A comparable atorvastatin 40mg is being sourced in Chile, and will be dispensed from the pharmacy of the Clínica Alemana de Santiago. Similarly, a comparable atorvastatin 40mg is being sourced in Hong Kong, and will be dispensed from the site's pharmacy.
Standard CareOther
Standard care for neurological symptoms as a result of COVID-19 infection.
| Study group | Role | What they receive |
|---|---|---|
| Study Medication Arm | Experimental | 6-monthly supplies of atorvastatin 40mg on top of standard care for a period of 12 months. Receives: Drug: Atorvastatin |
| Standard Care Arm | Active comparator | Standard care for a period of 12 months. Receives: Other: Standard Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurological Recovery
Processing speed, assessed on the oral Symbol Digit Modalities Test (SDMT)
Measured: 12 months
Secondary outcomes (1)
Brain Imaging
White matter free water measured on diffusion MRI brain imaging
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2021
- Study start10 Mar 2022
- Primary completion30 Jun 2025 (estimated)
- Study completion30 Jul 2025 (estimated)
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 Neurocognitive Impairment, MildStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 190 participants (actual)
Sponsor and investigators
- Lead sponsor
- The George Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sydney, Monash University, The Alfred, Universidad del Desarrollo, Chinese University of Hong Kong, Clinica Alemana de Santiago
- Responsible party
- Sponsor
- Investigators
- Craig Anderson, MD, Principal investigator, The George Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04904536
- Sponsor's protocol ID
- X21-0113
- Acronym
- STRONGER
- Status last verified
- Apr 2025
- First submitted
- 21 May 2021
- Last updated
- 10 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Delfino C, Carcel C, Lin X, Munoz-Venturelli P, Naismith SL, Woodward M, Peters R, Wijesuriya N, Law M, Harding IH, Wang X, Elliott J, Leder K, Hutchings O, Stecher X, Zoungas S, Anderson CS. STatin TReatment for COVID-19 to Optimise NeuroloGical recovERy (STRONGER): study protocol for a randomised, open label clinical trial in patients with persistent neurological symptoms after COVID-19 infection. BMJ Open. 2025 Apr 14;15(4):e089382. doi: 10.1136/bmjopen-2024-089382.
PubMed 40228860
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An International, Investigator Initiated and Conducted, Pragmatic Clinical Trial to Determine Whether 40mg Atorvastatin Daily Can Improve Neurocognitive Function in Adults With Long COVID Neurological Symptoms
- ClinicalTrials.gov ID
- NCT04904536
- Acronym / sponsor ID
- STRONGER / X21-0113
- Conditions
- Neurocognitive Impairment, Mild
- Keywords
- clinical trial, COVID-19, neurological symptoms, atorvastatin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 190 participants (actual)
- Lead sponsor
- The George InstituteUniversity, hospital or other
- Collaborators
- University of Sydney, Monash University, The Alfred, Universidad del Desarrollo, Chinese University of Hong Kong, Clinica Alemana de Santiago
- Study start
- 10 Mar 2022 (actual)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 30 Jul 2025 (estimated)
- First posted
- 27 May 2021 (actual)
- 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.
STRONGER is an international, investigator initiated and conducted, pragmatic clinical trial to determine whether 40mg atorvastatin daily can improve neurocognitive function in adults with long COVID neurological symptoms. The objective is to determine effectiveness of treatment with 40mg atorvastatin over 12 months on attenuating cognitive decline and neuroinflammatory biomarkers in adults with long COVID neurological symptoms. The study design is a prospective, randomised, open-label, blinded endpoint (PROBE) study of atorvastatin 40mg on top of standard care, in patients with long COVID neurological symptoms.
Detailed description
Question: Does treatment with 40mg atorvastatin over 12 months attenuate cognitive decline and neuroinflammatory biomarkers in adults with long COVID neurological symptoms? Aims: In 410 adults who report ongoing alteration of their memory, thinking, concentration or mood after COVID-19 diagnosis, this pragmatic clinical trial aims to determine the effects of standard-dose atorvastatin on improving neurological outcomes with sensitive measures of cognitive function and brain MRI.
Outcome measures include; Primary - processing speed, assessed on the oral Symbol Digit Modalities Test (SDMT). Key Secondary - white matter free water measured on diffusion MRI brain imaging. Other - other components of cognitive function; other health assessments; other MRI markers of cerebral white matter integrity, iron load, cerebral perfusion, and glutathione for oxidative stress; cost-effectiveness compared to standard care. The study sites are established at centralised research clinics located at: The Brain and Mind Centre of the University of Sydney; Alfred Medical Centre linked to Monash University, a research clinic associated with Clínica Alemana Universidad del Desarrollo, Santiago, Chile, and a research clinic associated with The Chinese University of Hong Kong. Additional sites may be set up as required.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study Medication Arm | Experimental | Drug: Atorvastatin6-monthly supplies of atorvastatin 40mg on top of standard care for a period of 12 months. |
| Standard Care Arm | Active comparator | Other: Standard CareStandard care for a period of 12 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥18 years
- History of COVID-19 that is confirmed by a positive polymerase-chain-reaction (PCR) test,rapid antigen test (RAT) or as per the state guidelines for COVID-19 diagnosis at the time of screening
- Any ongoing neurological symptoms as a result of COVID-19 (e.g. problems with memory, concentration, sleep disturbance and fatigue) that are identified through administration of the checklist of symptoms on the Somatic and Psychological Health Report (SPHERE) questionnaire, or reported loss of smell (anosmia)
- Able to fully participate in all procedures, including cognitive assessments
- Able and willing to provide written informed consent
Key exclusion criteria (9 listed)
- Evidence of dementia and/or significant cognitive impairment on screening (i.e: Blind Montreal Cognitive Assessment [MoCA] score <19/22 in conjunction with clinical assessment)
- Severe co-morbid medical or psychiatric condition that prevents participation
- History of traumatic brain injury with loss of consciousness (>30 mins) within the last 2 years
- Ongoing long-term use for a clear indication (e.g. secondary cardiovascular prevention in high-risk individuals) or any contraindication (e.g. previous adverse reaction) of statin use
- Evidence of severe or significant liver disease, defined as any of the following: acute viral hepatitis; chronic active hepatitis; chronic active hepatitis; cirrhosis; or elevated biochemical function markers i.e. ALT or AST >3x the ULN or eGFR <30mL/min/1.73m2
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 |
|---|---|---|
| Atorvastatin40mg atorvastatin + standard care daily for 12 months.Atorvastatin 40mg has TGA approval for general marketing for the treatment of hypercholesterolaemia and cardiovascular prevention under a number of manufacturer names.The study medication selected will be the atorvastatin 40mg (Apotex) which is scored, and allows down-titration to 20mg should a participant develop symptoms.The study medication will be packaged, labelled and dispensed directly to particpants by the Syntro Health pharmacy in Australia. A comparable atorvastatin 40mg is being sourced in Chile, and will be dispensed from the pharmacy of the Clínica Alemana de Santiago. Similarly, a comparable atorvastatin 40mg is being sourced in Hong Kong, and will be dispensed from the site's pharmacy. | Drug | Study Medication Arm |
| Standard CareStandard care for neurological symptoms as a result of COVID-19 infection. | Other | Standard Care Arm |
Primary outcome
Neurological Recovery
Time frame: 12 months
Processing speed, assessed on the oral Symbol Digit Modalities Test (SDMT)
1 secondary outcome
Brain Imaging
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2025.
- Derived from this study: PubMed 40228860Delfino C, Carcel C, Lin X, Munoz-Venturelli P, Naismith SL, Woodward M, Peters R, Wijesuriya N, Law M, Harding IH, Wang X, Elliott J, Leder K, Hutchings O, Stecher X, Zoungas S, Anderson CS. STatin TReatment for COVID-19 to Optimise NeuroloGical recovERy (STRONGER): study protocol for a randomised, open label clinical trial in patients with persistent neurological symptoms after COVID-19 infection. BMJ Open. 2025 Apr 14;15(4):e089382. doi: 10.1136/bmjopen-2024-089382.
Related trials for Neurocognitive Impairment, Mild
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingObservational study
Community-based Screening for Alzheimer's Disease
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
RecruitingObservational study
InRAD Observational Study
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
Recruiting
Treating Insomnia in Mild Cognitive Impairment
Mild Cognitive Impairment (MCI), Insomnia
Recruiting
Telehealth-Adapted Compensatory Training and Intervention for Cognition
MCI, Mild Cognitive Impairment
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.
Craig Anderson, MD principal investigator
The George Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Atorvastatin in people with Neurocognitive Impairment, Mild, run by The George Institute at 1 site in Australia.
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 9 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: under way, not looking for participants, as of the sponsor's last update on 10 Apr 2025. 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 Australia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Neurological Recovery (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 NCT04904536, 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 10 Apr 2025.