Clinical trial NCT05233579: Open-Label Trial of Sulforaphane in Premutation Carriers With FXTAS
Official title: Open-Label Trial of Sulforaphane in Premutation Carriers With FXTAS to Find Biomarkers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fragile X Associated Tremor/Ataxia Syndrome (Fxtas) (Diagnosis)
Keywords: Sulforaphane
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2022-02-10
Enrollment: 15
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: FXTAS is a rare genetic progressive neurodegenerative disorder, linked to a trinucleotide repeat expansion in the FMR1 gene. FXTAS is characterized by tremor and ataxia in addition to atrophy and white matter disease in the central nervous system (CNS). In addition to the major clinical observations of intention tremor and gait dysfunction, minor symptoms of parkinsonism, neuropathy, and cognitive decline also significantly impact individuals with FXTAS.

The dietary supplement being tested in this study is called Sulforaphane. It is found in broccoli and similar cruciferous vegetables and may cause some gas and discomfort. This is not a study looking at clinical efficacy but instead a study of molecular outcome measures. Investigators want to get more information about how Sulforaphane affects specific biomolecular markers captured in blood.

In this study, participants will be taking an increasing amount of the Sulphoraphane supplement pills (238mg/tablet), starting at 1 and increasing to 6, every morning at breakfast for 6 months. In addition, there will be a total of 3 visits (Initial, 3-month and 6-month) to the MIND Institute where participants will be evaluated. At each visit (3 total) participants will undergo a battery of medical and neurologic exams which make take 2-3 days to complete each time. Participants and/or their caregivers will also be asked to fill out questionnaires/surveys. At the initial visit and at 6 months, we will collect blood for analysis. Two MRI scans will be done, also at the initial visit and at 6 months.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of FXTAS
* Presence of a FMR1 premutation (55 to 200 CGG repeats)

Exclusion Criteria:

* Individuals with severe renal failure (GFR is \<60 ml/min/1.73 m\^2)
* Significant and current reported substance abuse
* Individuals with substance use disorder (meets 6 or more symptoms of substance use disorder criteria)
* Any subject on hospice or on home oxygen
* Individuals who are pregnant

Primary outcomes:
measure: Changes in mitochondrial function via mitochondrial membrane potential and mass.
timeFrame: Baseline, 6 months
measure: Changes in mitochondrial function via ATP production
timeFrame: Baseline, 6 months
measure: Observing changes in candidate molecular biomarkers in FXTAS and mitochondrial dysregulation: GRP78
timeFrame: Baseline, 6 months
measure: Observing changes in candidate molecular biomarkers in FXTAS and mitochondrial dysregulation: CHOP level
timeFrame: baseline, 6 months
measure: Observing changes in candidate molecular biomarkers in FXTAS and mitochondrial dysregulation: Bax/Bcl-2 ratio
timeFrame: baseline, 6 months
Secondary outcomes:
measure: Changes in clinical staging of FXTAS
timeFrame: Baseline, 6 months
measure: Changes in subcortical brain structures damaged in FXTAS through MRI imaging
timeFrame: Baseline, 6 months
measure: Changes in FLAIR hypersensitivity volume for subcortical lesions
timeFrame: Baseline, 6 months
measure: Changes in Neurological Quality of Life using the Neuro-QoL upper extremity function fine motor scale
timeFrame: Baseline, 6 months
measure: Changes in Neurological Quality of Life using the Neuro-QoL lower extremity functioning mobility scale
timeFrame: Baseline, 6 months
measure: Changes in psychological Issues
timeFrame: Baseline, 6 months
measure: Changes in Grip Strength
timeFrame: Baseline, 6 months
measure: Changes in gait variability
timeFrame: Baseline, 6 months
measure: Changes in dexterity, tremor, and bradykinesia abnormalities
timeFrame: Baseline, 6 months
measure: Changes in kinetic, postural, and rest tremor upper extremity bradykinesia, hypokinesia, dysrhythmia, and dyskinesias
timeFrame: Baseline, 6 months
measure: Changes in cognitive dysfunction using MoCA
timeFrame: Baseline, 6 months
measure: Changes in cognitive dysfunction using MMSE
timeFrame: Baseline, 6 months
measure: Changes in executive function deficits using BDS-2
timeFrame: Baseline, 6 months
measure: Changes in executive function deficits using COWAT
timeFrame: Baseline, 6 months
measure: Changes in frontal executive planning
timeFrame: Baseline, 6 months
measure: Changes in Hippocampus-mediated memory deficits
timeFrame: Baseline, 6 months
measure: Changes in motor movements
timeFrame: Baseline, 6 months
measure: Changes in cognitive ability
timeFrame: Baseline
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis MIND Institute
state: California
Study officials:
References:
citation: Napoli E, Flores A, Mansuri Y, Hagerman RJ, Giulivi C. Sulforaphane improves mitochondrial metabolism in fibroblasts from patients with fragile X-associated tremor and ataxia syndrome. Neurobiol Dis. 2021 Sep;157:105427. doi: 10.1016/j.nbd.2021.105427. Epub 2021 Jun 19.
citation: Uddin MS, Mamun AA, Jakaria M, Thangapandiyan S, Ahmad J, Rahman MA, Mathew B, Abdel-Daim MM, Aleya L. Emerging promise of sulforaphane-mediated Nrf2 signaling cascade against neurological disorders. Sci Total Environ. 2020 Mar 10;707:135624. doi: 10.1016/j.scitotenv.2019.135624. Epub 2019 Nov 21.
citation: Berry-Kravis EM, Harnett MD, Reines SA, Reese MA, Ethridge LE, Outterson AH, Michalak C, Furman J, Gurney ME. Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: a randomized, placebo-controlled, phase 2 clinical trial. Nat Med. 2021 May;27(5):862-870. doi: 10.1038/s41591-021-01321-w. Epub 2021 Apr 29.