Clinical trial NCT05416515: A Study of Fisetin to Treat Carpal Tunnel Syndrome
Official title: Phase 2 Clinical Trial of FIsetin to Treat CArpal Tunnel Syndrome (FITCATS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Carpal Tunnel Syndrome
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2022-06-13
Enrollment: 40
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is being conducted to investigate the safety and effectiveness of the drug Fisetin for mild or moderate carpal tunnel syndrome (CTS).

Detailed description: FITCATS trial will enroll approximately 40 subjects with mild-moderate CTS and evidence of senescence from blood markers into a short term (180 days) prospective phase 2 study of Fisetin therapy, using as outcome measures a well-accepted patient reported outcome questionnaire (Boston CTS questionnaire, BCTQ) as well as reduction from baseline in senescence markers in the blood, including SASP factors and inflammatory markers. Based on the known performance of the BCTQ, the investigators estimate that a sample size of 40 will be sufficient to show a clinically important difference in outcome, if it is present. Each subject will be enrolled for a six-month period. Subjects may withdraw at any time, for any reason.

Eligibility criteria: 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 one hand 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 will have 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 pregnancy test at screening (serum) and before the first dose on Day 1 (urine), before the 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 to take appropriate precautions to avoid pregnancy from screening until 30 days after the last dose of study drug (day 60). Permitted methods in preventing pregnancy (see Appendix A) will be communicated to the participants and their compliance confirmed.
  * All female participants of childbearing potential will refrain from donating oocytes from screening-day 60 of the study.
  * Women without child bearing potential (ie., surgically sterile with hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible to participate without the above precautions.
* Willing and able to comply with study procedures and requirements and attend all study 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 wrist within the past 6 months.
* Prisoners, institutionalized individuals, or others who may be considered vulnerable populations, 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, or alanine aminotransferase (ALT) \> 4 X upper limit of normal as a marker of liver disease
* 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 ≤1 x 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 diabetic control
* Creatinine \>2.5, cystatin c \>3 or eGFR\< 25 ml/min/1.73 m2 as a marker of advanced kidney 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 clinical judgement
* Any of the following clinical diagnosis or conditions: cervical radiculopathy, renal failure (see laboratory exclusion criteria), liver disease (see laboratory exclusion criteria), peripheral nerve disease, uncontrolled diabetes (see laboratory exclusion criteria), 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 any flavonoid as a nutritional supplement. Note that consuming foods rich in flavonoids is NOT an exclusion, both because flavonoids are present in almost all fruits and vegetables, making such an exclusion impossible as a practical matter, and, from a scientific perspective, the amount of flavonoids in general, and Fisetin in particular, present in foods is far lower than the dose that will be administered in the trial.
* Patients currently taking medications listed in the Investigator Brochure are excluded unless medication can be safely held following the guidelines in the Investigator Brochure.
* If the patient is required to initiate any medication listed in the Investigator Brochure during the study, the PI will reassess their continued participation in the study.

Primary outcomes:
measure: Change in CTS symptoms
timeFrame: Baseline, 60 days
Secondary outcomes:
measure: percent decrease in blood markers of cellular senescence, e.g., p16, IL-6, IL-15, TNF, PAI-1, ICAM-1, and additional exploratory, novel assays
timeFrame: Baseline, 60 days
measure: percent decrease in blood markers of cellular senescence in long-term
timeFrame: Baseline, 180 days
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Peter C Amadio, MD
role: PRINCIPAL_INVESTIGATOR
References: