CadasilPhase 2NCT04658823
Efficacy and Safety of Tocotrienols in CADASIL
A Phase 2 study testing HOV-12020 (Palm tocotrienols complex) in people with Cadasil, run by Hovid Berhad at 1 site in France.
Trial summary
CADASIL is a paradigmatic cerebral small vessel disease responsible for white-matter lesions, accumulation of lacunes, microbleeds and cerebral atrophy. The disease is responsible for stroke and cognitive decline associated with motor disability. Read more about this study
- Who is it for?
- Ages 45 to 75 years
- Conditions the study is for
- Cadasil
- What is being tested?
- HOV-12020 (Palm tocotrienols complex)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 21 Dec 2020to 31 Oct 2024
- Phase
- Phase 2
- 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 45 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female
- Participants aged 45 to 75 years inclusive, at the time of signing of informed consent
- Confirmed Diagnosis of CADASIL, defined by either:
- A Typical mutation in the NOTCH3 gene responsible for an odd number of cystein residue OR
- A positive skin biopsy showing typical granular osmiophilic material (GOM) in the vascular wall of small vessels with electron microscopy
- Presence of at least one prevalent lacune on the MRI identified on 3DT1 or FLAIR images.
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- Presence of Confluent white matter hyperintensities (WMH) on T2-weighted or FLAIR MR images (Fazekas grade 2-3).
- MMSE score ≥15
- mRS at 0 - 3
- A woman of child bearing potential (WOCBP) is eligible to participate if she is not pregnant, not breastfeeding, and agrees to follow contraceptive guidance (as described in Appendix 5) provided by the study clinician during the treatment period and for 28 days after the last dose of the study treatment.
- Capable of giving signed informed consent and have a patient representative willing to co-sign informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Who cannot join
- Clinical stroke with persisting neurological deficit within 6 months prior to Screening.
- Any other neurodegenerative disorder, such as Parkinson's disease, Alzheimer's disease, or Huntington's disease.
- Current significant hematological, cardiac, pulmonary, metabolic, neurologic or psychiatric disorders, uncontrolled seizures, untreated hypertension, disorders increasing risk of bleeding (Hemophilia), or any other significant active medical condition which in the Investigator's opinion would impact participation in this study.
- History of myocardial infarction within 3 months prior to Screening, or current active angina pectoris, or symptomatic heart failure.
- History of cancer, within the past 5 years. Patients with basal cell carcinoma, squamous cell carcinoma, and Stage 1 prostate cancer can be included in the study.
- An episode of major depression within the last 6 months prior to Screening (clinically stable minor depression is not exclusionary).
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- History of attempted suicide within 6 months prior to Screening or a positive response to items 4 or 5 of Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening and Baseline.
- History of drug or alcohol abuse or dependence.
- Contra-indications to MRI: presence of a pacemaker, severe claustrophobia, cochlear implants, ferromagnetic devices or clips, intracranial vascular clips, insulin pumps, metallic implants.
- Pregnancy or breastfeeding women.
- History of human immunodeficiency virus (HIV), hepatitis B or C.
- History of allergy or severe intolerance to Vitamin E (tocopherols / tocotrienols).
- Presence at Screening of alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, or lipase 2x above the upper limit of normal (ULN) of laboratory reference range, total bilirubin 1.5x ULN, any other clinically significant laboratory abnormality.
- Presence at Screening of Creatinine clearance <60 (estimated by Cockcroft-Gault equation).
- Cognitive enhancers such as donepezil, are allowed only if stable dosage within 3 months prior to Screening.
- Use of tocotrienol supplementation within 3 months prior to Screening or any current use of Vitamin E other than study drug (all other vitamin supplements are allowed, if stable dosage within 3 months prior to screening).
- Participation in a clinical trial with investigational product (IP) within 30 days prior to Screening. Patients participating in observational studies with no IP, will be allowed to participate in this study
- Indication for anti-coagulant therapy
- Patients with known sensitivity to polyoxyl castor oil or risk of allergy to soybean and peanuts.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Placebo-controlled Double-blind Pilot / Phase II Study to Assess the Efficacy and Safety of HOV-12020 in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)
CADASIL is a paradigmatic cerebral small vessel disease responsible for white-matter lesions, accumulation of lacunes, microbleeds and cerebral atrophy. The disease is responsible for stroke and cognitive decline associated with motor disability. The number of incident lacunes, and amount of cerebral atrophy were recently found to have a strong relationship to cognitive decline and disability progression over 3 years in a large sample of patients. Palm tocotrienols has previously shown evidence of therapeutic effect in attenuating the progression of WMH related to sporadic cerebral small vessel disease in a randomized controlled clinical trial. We hypothesize that palm tocotrienols complex (HOV-12020) can reduce the clinical progression in CADASIL.
- Conditions
- Cadasil
- Being tested
- HOV-12020 (Palm tocotrienols complex), Placebo
- Keywords
- CADASIL, Tocotrienols, Vitamin E, Vascular, Stroke, Dementia, Cerebral Small Vessel Disease, Cognitive disorder, Neurovascular disease, Hereditary multi-infarct, Cerebrovascular disease
- Medical subject headings
- CADASIL, Stroke, Dementia, Cerebral Small Vessel Diseases, Cognitive Dysfunction, Cerebrovascular Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HOV-12020 (Palm tocotrienols complex)Drug
Also called HOV-12020, Palm Vitamin E, Tocotrienols, Tocovid Suprabio
Oral Softgel capsule containing mixed tocotrienols and tocopherol with enhanced absorption delivery system; 1 capsule twice daily
PlaceboDrug
Oral Softgel capsule containing soybean oil; 1 capsule twice daily
| Study group | Role | What they receive |
|---|---|---|
| HOV-12020 | Experimental | Palm tocotrienols complex Oral softgel capsule (containing 285mg mixed tocotrienols and tocopherol) Receives: Drug: HOV-12020 (Palm tocotrienols complex) |
| PLACEBO | Placebo comparator | Placebo Oral Softgel capsule (each capsule containing vitamin E stripped soybean oil) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of manifestations related to clinical worsening
Occurrence one failure event within 24 months after Baseline. A failure event is considered when at least one of the following manifestations is detected during the study period:
- incident stroke
- increase of disability corresponding to an increase in the mRS score of at least 1 point to result in a score of 2 or greater
- cognitive decline corresponding to a reduction of at least 4 points of the VADAS-Cog score
Measured: 24 months
Secondary outcomes (1)
Incidence of adverse events
Number of serious AEs, type of severe AEs, Total number of AEs
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2020
- Study start21 Dec 2020
- Primary completion28 Feb 2024
- Study completion31 Oct 2024
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 CadasilStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hovid Berhad
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pr Hugues Chabriat, Principal investigator, Hôpital Lariboisière APHPDavid Ho, Study director, Hovid Berhad
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04658823
- Sponsor's protocol ID
- T3-CAD-01
- Status last verified
- Jan 2026
- First submitted
- 29 Nov 2020
- Last updated
- 2 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chabriat H, Biard L, Guey S, Alili N, Machado C, Jabouley A, Reyes S, Lebenberg J, Guillonnet A, Dubus E, Taleb A, Julien F, Dias-Gastellier N, Fernandes F, Jouvent E, Herve D. Tocotrienol-rich vitamin E complex in CADASIL (T3CAD): a randomised, double-blind, placebo-controlled trial. EClinicalMedicine. 2026 Mar 30;94:103853. doi: 10.1016/j.eclinm.2026.103853. eCollection 2026 Apr.
PubMed 42005919
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo-controlled Double-blind Pilot / Phase II Study to Assess the Efficacy and Safety of HOV-12020 in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)
- ClinicalTrials.gov ID
- NCT04658823
- Acronym / sponsor ID
- T3-CAD-01
- Conditions
- Cadasil
- Keywords
- CADASIL, Tocotrienols, Vitamin E, Vascular, Stroke, Dementia, Cerebral Small Vessel Disease, Cognitive disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Hovid BerhadIndustry (pharma, biotech, devices)
- Study start
- 21 Dec 2020 (actual)
- Primary completion
- 28 Feb 2024 (actual)
- Study completion
- 31 Oct 2024 (actual)
- First posted
- 9 Dec 2020 (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.
CADASIL is a paradigmatic cerebral small vessel disease responsible for white-matter lesions, accumulation of lacunes, microbleeds and cerebral atrophy. The disease is responsible for stroke and cognitive decline associated with motor disability. The number of incident lacunes, and amount of cerebral atrophy were recently found to have a strong relationship to cognitive decline and disability progression over 3 years in a large sample of patients. Palm tocotrienols has previously shown evidence of therapeutic effect in attenuating the progression of WMH related to sporadic cerebral small vessel disease in a randomized controlled clinical trial. We hypothesize that palm tocotrienols complex (HOV-12020) can reduce the clinical progression in CADASIL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HOV-12020 | Experimental | Drug: HOV-12020 (Palm tocotrienols complex)Palm tocotrienols complex Oral softgel capsule (containing 285mg mixed tocotrienols and tocopherol) |
| PLACEBO | Placebo comparator | Drug: PlaceboPlacebo Oral Softgel capsule (each capsule containing vitamin E stripped soybean oil) |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female
- Participants aged 45 to 75 years inclusive, at the time of signing of informed consent
- Confirmed Diagnosis of CADASIL, defined by either:
- Presence of at least one prevalent lacune on the MRI identified on 3DT1 or FLAIR images.
- Presence of Confluent white matter hyperintensities (WMH) on T2-weighted or FLAIR MR images (Fazekas grade 2-3).
Key exclusion criteria (19 listed)
- Clinical stroke with persisting neurological deficit within 6 months prior to Screening.
- Any other neurodegenerative disorder, such as Parkinson's disease, Alzheimer's disease, or Huntington's disease.
- Current significant hematological, cardiac, pulmonary, metabolic, neurologic or psychiatric disorders, uncontrolled seizures, untreated hypertension, disorders increasing risk of bleeding (Hemophilia), or any other significant active medical condition which in the Investigator's opinion would impact participation in this study.
- History of myocardial infarction within 3 months prior to Screening, or current active angina pectoris, or symptomatic heart failure.
- History of cancer, within the past 5 years. Patients with basal cell carcinoma, squamous cell carcinoma, and Stage 1 prostate cancer can be included in the study.
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 |
|---|---|---|
| HOV-12020 (Palm tocotrienols complex)Also: HOV-12020, Palm Vitamin E, Tocotrienols, Tocovid SuprabioOral Softgel capsule containing mixed tocotrienols and tocopherol with enhanced absorption delivery system; 1 capsule twice daily | Drug | HOV-12020 |
| PlaceboOral Softgel capsule containing soybean oil; 1 capsule twice daily | Drug | PLACEBO |
Primary outcome
Incidence of manifestations related to clinical worsening
Time frame: 24 months
Occurrence one failure event within 24 months after Baseline. A failure event is considered when at least one of the following manifestations is detected during the study period: * incident stroke * increase of disability corresponding to an increase in the mRS score of at least 1 point to result in a score of 2 or greater * cognitive decline corresponding to a reduction of at least 4 points of the VADAS-Cog score
1 secondary outcome
Incidence of adverse events
Time frame: 24 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 2 Feb 2026.
- Derived from this study: PubMed 42005919Chabriat H, Biard L, Guey S, Alili N, Machado C, Jabouley A, Reyes S, Lebenberg J, Guillonnet A, Dubus E, Taleb A, Julien F, Dias-Gastellier N, Fernandes F, Jouvent E, Herve D. Tocotrienol-rich vitamin E complex in CADASIL (T3CAD): a randomised, double-blind, placebo-controlled trial. EClinicalMedicine. 2026 Mar 30;94:103853. doi: 10.1016/j.eclinm.2026.103853. eCollection 2026 Apr.
- Individual participant dataSharing planned: No
Related trials for Cadasil
RecruitingObservational study
Registry for CADASIL
Cerebral Autosomal Dominant Ateriopathy With Subcortical Infarcts and Leukoencephalopathy
RecruitingObservational study
Natural History Study of CADASIL
Cardiovascular Disease, Arterial Stiffness
RecruitingObservational study
The Erlanger Stroke Registry (ESPro) is the Only Ongoing Prospective Population-based Stroke Registry in Germany, Started in 1994. ESPro Includes All Hospitalized and Non-hospitalized Patients With Stroke in the Community of Erlangen (120.000 Inhabitants), With a Long-life Follow-up.
Intracerebral Haemorrhage (ICH), Cerebral Infarction
Active, not recruitingObservational study
Florida Cerebrovascular Disease Biorepository and Genomics Center
Cerebrovascular Disease, Ischemic Stroke
RecruitingObservational study
Effect of the Mediterranean Diet in Patients Affected by CADASIL and Cerebral Amyloid Angiopathy.
Cerebral Amyloid Angiopathy, CAA - Cerebral Amyloid Angiopathy
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.
Pr Hugues Chabriat principal investigator
Hôpital Lariboisière APHP
David Ho study director
Hovid Berhad
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HOV-12020 (Palm tocotrienols complex) in people with Cadasil, run by Hovid Berhad at 1 site in France.
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 11 inclusion and 19 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 2 Feb 2026. 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 France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Incidence of manifestations related to clinical worsening (time frame: 24 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 NCT04658823, 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 2 Feb 2026.