Investigating the effect of glycerol phenylbutyrate on neurofilament levels in patients with corticobasal syndrome

Double-blind, Randomised, Prospective, Placebo Controlled Parallel Group Phase II Study to Investigate the Effect of Glycerol Phenylbutyrate (GPB) on Neurofilament Light Chain (NfL) Levels in Patients With Corticobasal Syndrome (CBS)

This study is testing if glycerol phenylbutyrate can lower certain markers of disease progression in adults with corticobasal syndrome.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Technical University of Munich (Academic / other)
• Locations: 2 sites (Munich, Bavaria and 1 other locations)
• Trial ID: NCT05983588 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the potential disease-modifying effects of glycerol phenylbutyrate (GPB) in patients diagnosed with corticobasal syndrome (CBS). Over a 26-week period, participants will receive either GPB or a placebo, with the primary outcome being the measurement of neurofilament light chain (NfL) levels in plasma, which serves as a biomarker for disease progression. The study focuses on understanding how GPB may influence neuroinflammation and microglial function, which are critical in the pathogenesis of CBS. The trial is designed for adults aged 18 and older who meet specific diagnostic criteria for CBS.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with a clinical diagnosis of possible or probable corticobasal syndrome.

Not a fit: Patients who have regularly consumed glycerol phenylbutyrate in the last six months or those with other neurodegenerative disorders not specified in the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new disease-modifying therapy for patients suffering from corticobasal syndrome.

How similar studies have performed: While there is strong evidence supporting the role of phenylbutyrate in modulating neuroinflammation, this specific approach in corticobasal syndrome is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Age: ≥ 18 years
2. "clinical possible" or "clinical probable" CBS (Armstrong et al., Neurol-ogy, 2013 80;496-503) and patients with Progressive Supranuclear Palsy-CBS according to Höglinger et al. (Mov Disord. 2017 Jun;32(6):853-864)
3. No regular consumption of glycerol phenylbutyrate within the last 6 months prior to V1
4. Capable of thoroughly understanding all information given and giving full informed consent according to GCP
5. Capability and willingness to comply with the procedures of the clinical trial
6. Women of childbearing age must be non-lactating and surgically sterile or using a highly effective method of birth control and have a nega-tive pregnancy test. In case of using a hormonal contraception, the method must be supplemented with a barrier method (preferably male condom). Acceptable methods of birth control with a low failure rate i.e. less than 1% per year when used consistently and correct are such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence (defined as refraining from heterosexual intercourse during the clinical trial) or vasectomized partner. Unacceptable birth control methods are: periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only and lactational amenorrhoea method (LAM). Female condom and male condom should not be used together.
7. A stable regimen for at least 1 month prior to V1 and no foreseeable need to change the regimen throughout the 26 week treatment period for

   1. drugs acting against Parkinsonism (e.g. Levodopa, Dopamine-Agonists, Amantadine and MAO-B-Inhibitors)
   2. other CNS-active substances including e.g. antidepressants and antidementia drugs

Exclusion Criteria:

1. Neurodegenerative diseases other than CBS
2. Underlying Alzheimer's pathology as defined by positive β-amyloid-PET or reduced Aβ 1-42 in CSF
3. Participation in another clinical trial involving administration of an investigational medicinal product within 1 month or 5 half-lives of the investigational medicinal product, whichever is longer, prior to V1
4. Known hypersensitivity to glycerol phenylbutyrate or its further components, or to drugs with a similar chemical structure or to any of the components of the placebo
5. Treatment with valproic acid, haloperidol or probenecid
6. A physical or psychiatric condition (e.g. frontal lobe syndrome, psychotic disorder or major depression), which at the investigator's discretion may put the subject at risk, may confound the trial results or may interfere with the subject's participation in this clinical trial
7. Persistent abuse of medication, drugs or alcohol
8. Current or planned pregnancy or breast-feeding in females
9. Other severe medical conditions upon the discretion of the investigator

Where this trial is running

Munich, Bavaria and 1 other locations

• Klinikum der Universität München (KUM), Campus Großhadern, Klinik und Poliklinik für Neurologie & German Center for Neurodegenerative Diseases (DZNE), Department of Neurology — Munich, Bavaria, Germany (Recruiting)
• Klinikum rechts der Isar Technische Universität München Klinik und Poliklinik für Neurologie & German Center for Neurodegenerative Diseases (DZNE), Department of Neurology — Munich, Bavaria, Germany (Recruiting)

Study contacts

• Study coordinator: Johannes Prof. Dr. Levin

Conditions Corticobasal Syndrome