A Study of Fisetin to Treat Carpal Tunnel Syndrome

Subjects must meet all of the following inclusion criteria to be eligible for enrollment:

Inclusion Criteria:

• Males and females between age 21 and 80 years of age.

• Symptoms of numbness or tingling for at least 4 weeks in at least two digits on onehand that include thumb, index, long, or radial border of ring finger.

• Classic or probable carpal tunnel syndrome on Katz-Stirrat hand diagram.

• A clinical diagnosis of carpal tunnel syndrome. Patients with bilateral CTS willhave the more severe hand enrolled.

• Able to complete English-language questionnaires and clinical evaluations.

• Willingness to avoid pregnancy.

• Female participants of childbearing potential must have a negative pregnancytest at screening (serum) and before the first dose on Day 1 (urine), beforethe third dose on Day 29 (urine), and 60 days after the final dose on day 60 (urine).

• Sexually active female participants of childbearing potential must agree totake appropriate precautions to avoid pregnancy from screening until 30 daysafter the last dose of study drug (day 60). Permitted methods in preventingpregnancy (see Appendix A) will be communicated to the participants and theircompliance confirmed.

• All female participants of childbearing potential will refrain from donatingoocytes from screening-day 60 of the study.

• Women without child bearing potential (ie., surgically sterile withhysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible toparticipate without the above precautions.

• Willing and able to comply with study procedures and requirements and attend allstudy visits as defined in this protocol.

Exclusion Criteria

Subjects with any of the following exclusion criteria will not be eligible for enrollment:

General Exclusion Criteria:

• Unable or unwilling to give informed consent.

• Pregnant or breast feeding

• Previous carpal tunnel release on the study hand

• History of steroid injection into carpal tunnel or surgery on the affected wristwithin the past 6 months.

• Prisoners, institutionalized individuals, or others who may be considered vulnerablepopulations, such as individuals with dementia.

Laboratory Exclusion Criteria:

The following laboratory tests as indicated or as per clinical judgement:

• Bilirubin > 2.0; serum aspartate transaminase (AST) > 4 X upper limit of normal, oralanine aminotransferase (ALT) > 4 X upper limit of normal as a marker of liverdisease

• Hemoglobin < 7g/dL; white blood cell count ≤2,000/mm3 (≤2.0 x 109/L) or ≥20,000/mm3 (≥20 x 109/L); platelet count ≤40,000/μL (≤40 x 109/L); absolute neutrophil count ≤1x 109/L; lymphocyte count <0.3 x 109/L at screening as a marker of poor nutrition

• Plasma and/or serum fasting glucose > 300 or HbA1c > 9 as a marker of poor diabeticcontrol

• Creatinine >2.5, cystatin c >3 or eGFR< 25 ml/min/1.73 m2 as a marker of advancedkidney disease,

• CRP > 10 or ESR >25 as a marker of systemic inflammation

• Unstable (as per clinical judgement) major cardiovascular, renal, endocrine,immunological, or hepatic disorder

Clinical History Exclusion Criteria

• History of diverticulitis or diverticulosis with GI bleeding, as per clinicaljudgement

• Any of the following clinical diagnosis or conditions: cervical radiculopathy, renalfailure (see laboratory exclusion criteria), liver disease (see laboratory exclusioncriteria), peripheral nerve disease, uncontrolled diabetes (see laboratory exclusioncriteria), or other metabolic disorder; as per clinical judgement

• Human immunodeficiency virus infection

• Known active hepatitis B or C infection

• Invasive fungal infection

• Uncontrolled (as per clinical judgement) pleural/pericardial effusions or ascites

• New/active invasive cancer except non-melanoma skin cancers

Medication Exclusion Criteria

• Known hypersensitivity or allergy to Fisetin or other flavonoids

• Currently participating in another study using Fisetin or currently taking anyflavonoid as a nutritional supplement. Note that consuming foods rich in flavonoidsis NOT an exclusion, both because flavonoids are present in almost all fruits andvegetables, making such an exclusion impossible as a practical matter, and, from ascientific perspective, the amount of flavonoids in general, and Fisetin inparticular, present in foods is far lower than the dose that will be administered inthe trial.

• Patients currently taking medications listed in the Investigator Brochure areexcluded unless medication can be safely held following the guidelines in theInvestigator Brochure.

• If the patient is required to initiate any medication listed in the InvestigatorBrochure during the study, the PI will reassess their continued participation in thestudy.