- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04658823
Efficacy and Safety of Tocotrienols in CADASIL
March 22, 2022 updated by: Hovid Berhad
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
50
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Paris, France, 75010
- Hôpital Lariboisière APHP
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
45 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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).
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: HOV-12020
Palm tocotrienols complex Oral softgel capsule (containing 285mg mixed tocotrienols and tocopherol)
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Oral Softgel capsule containing mixed tocotrienols and tocopherol with enhanced absorption delivery system; 1 capsule twice daily
Other Names:
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Placebo Comparator: PLACEBO
Placebo Oral Softgel capsule (each capsule containing vitamin E stripped soybean oil)
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Oral Softgel capsule containing soybean oil; 1 capsule twice daily
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of manifestations related to clinical worsening
Time Frame: 24 months
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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:
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24 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events
Time Frame: 24 months
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Number of serious AEs, type of severe AEs, Total number of AEs
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24 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change of cognitive performance on CDR
Time Frame: 24 months
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Individual variation of different cognitive measures obtained using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB); score 0 to 18
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24 months
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Change of cognitive performances on MDRS
Time Frame: 24 months
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Individual variation of different cognitive measures obtained using the Mattis Dementia Rating Scale (MDRS); score 0 to 144
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24 months
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Change of cognitive performances on sub-subscale of MDRS
Time Frame: 24 months
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Individual variation of different cognitive measures obtained using the initiation/perseveration subscale of the MDRS (MDRS-I/P); score 0 to 37
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24 months
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Change of cognitive performances on TMT
Time Frame: 24 months
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Individual variation of different cognitive measures obtained using the Trail Making Test Part A and B time
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24 months
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Changes of gait and balance performances on SPPB
Time Frame: 24 months
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Between group difference on individual changes of the Short Physical Performance Battery (SPPB) score; score 0 (worst) to 12 (best)
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24 months
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Effects on Quality of life using SF3-6
Time Frame: 24 months
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Between group differences in patient reported outcomes as assessed by the Short Form-36 (SF-36), score 0 to 100
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24 months
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Effects on Quality of life, using DAD
Time Frame: 24 months
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Between group differences in patient reported outcomes as assessed by the Disability Assessment for Dementia (DAD) scores; score 0 to 100
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24 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Pr Hugues Chabriat, Hôpital Lariboisière APHP
- Study Director: David Ho, Hovid Berhad
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 21, 2020
Primary Completion (Anticipated)
December 31, 2023
Study Completion (Anticipated)
December 31, 2023
Study Registration Dates
First Submitted
November 29, 2020
First Submitted That Met QC Criteria
December 7, 2020
First Posted (Actual)
December 9, 2020
Study Record Updates
Last Update Posted (Actual)
March 24, 2022
Last Update Submitted That Met QC Criteria
March 22, 2022
Last Verified
March 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Ischemia
- Pathologic Processes
- Necrosis
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Genetic Diseases, Inborn
- Brain Ischemia
- Dementia
- Infarction
- Stroke
- Brain Infarction
- Cerebral Arterial Diseases
- Intracranial Arterial Diseases
- Cerebral Small Vessel Diseases
- Cerebral Infarction
- Dementia, Vascular
- CADASIL
- Dementia, Multi-Infarct
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Protective Agents
- Micronutrients
- Vitamins
- Antioxidants
- Vitamin E
- Tocopherols
- Tocotrienols
- Tocovid
Other Study ID Numbers
- T3-CAD-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cadasil
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National Heart, Lung, and Blood Institute (NHLBI)CompletedCardiovascular Disease | Arterial Stiffness | Germline Mutation in the NOTCH 3 Gene | Pathogenesis of CADASIL | Clinical Phenotype of CADASILUnited States
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National Heart, Lung, and Blood Institute (NHLBI)RecruitingCardiovascular Disease | Arterial Stiffness | Germline Mutation in the NOTCH 3 Gene | Pathogenesis of CADASIL | Clinical Phenotype of CADASILUnited States
-
Ever Neuro Pharma GmbHXClinical GmbH; idv Datenanalyse & VersuchsplanungRecruiting
-
Perminder SachdevMelbourne Health; Royal Brisbane and Women's Hospital; The University of Queensland and other collaboratorsRecruiting
-
National Cerebral and Cardiovascular Center, JapanCompleted
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Assistance Publique - Hôpitaux de ParisRecruitingCadasil | Angiopathy; CerebralFrance
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Peking University First HospitalChinese Academy of SciencesRecruiting
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Assistance Publique - Hôpitaux de ParisNot yet recruitingCerebral Small Vessel Diseases | CADASIL (Diagnosis)
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Mayo ClinicWithdrawnMigraine | Cadasil
Clinical Trials on HOV-12020 (Palm tocotrienols complex)
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National Neuroscience InstituteHovid BerhadRecruiting
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Universiti Sains MalaysiaMalaysia Palm Oil Board; Avantsar Sdn. Bhd.Terminated
-
University of California, Los AngelesTerminatedHypercholesterolemiaUnited States
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Universiti Sains MalaysiaMalaysia Palm Oil BoardCompletedCerebrovascular DisordersMalaysia
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Malaysia Palm Oil BoardUniversiti Putra MalaysiaCompletedMetabolic Syndrome | Platelet Aggregation, SpontaneousMalaysia
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University of California, Los AngelesWithdrawnCholesterol LoweringUnited States
-
Vanderbilt UniversityCompletedChronic Kidney DiseaseUnited States
-
Vanderbilt UniversityFresenius Medical Care North AmericaCompleted
-
Augusta UniversityActive, not recruitingCystic FibrosisUnited States
-
Chi Mei Medical HospitalCompleted