Targeting Cellular Senescence With Senolytics to Improve Skeletal Health in Older Humans

NCT04313634 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 18-010546
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

To determine if senolytic drugs reduce senescent cell burden and reduce bone resorption markers/increase bone formation markers in elderly women.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Change in C-terminal Telopeptide of Type I Collagen [CTX]

  Percent change in serum bone turnover markers C-terminal telopeptide of type I collagen \[CTX\]. The C-terminal telopeptide (CTX), also known as carboxy-terminal collagen crosslinks, is a biomarker used to measure the rate of bone turnover. It provides valuable information for assessing bone health and evaluating treatment responses.

  Baseline, 20 weeks

Secondary Outcomes (5)

• Change in Bone Turnover Markers

  Baseline, 2 weeks

• Change in Bone Turnover Markers

  Baseline, 4 weeks

• Change in Bone Turnover Markers

  Baseline, 20 weeks

• Change in Bone Mineral Density (BMD)

  Baseline, 20 weeks

• Change in Plasma Senescence-associated Secretory Phenotype (SASP)

  Baseline, 2 weeks

Study Arms (3)

Dasatinib plus Quercetin Treatment Goup

EXPERIMENTAL

Subjects will receive Dasatinib (D; 100 mg for two days) plus Quercetin (Q; 1000 mg total daily for three consecutive days taken orally on an intermittent schedule (starting every 28 days) with no-therapy periods in between dosing regimens, repeated every 28 days over 20 weeks, resulting in five total dosing periods throughout the entire intervention

Drug: Dasatinib; Drug: Quercetin

Fisetin Treatment Group

EXPERIMENTAL

Subjects will receive Fisetin (F; \~20 mg/kg/day for three consecutive days) taken orally on an intermittent schedule (starting every 28 days) with no-therapy periods in between dosing regimens, repeated every 28 days over 20 weeks, resulting in five total dosing periods throughout the entire intervention

Drug: Fisetin

Untreated Control Group

NO INTERVENTION

Subjects will not receive any intervention

Interventions

Dasatinib DRUG

Dasatinib will be supplied as 100 mg tablet white to off-white, biconvex, oval, film- coated

Also known as: Sprycel

Dasatinib plus Quercetin Treatment Goup

Quercetin DRUG

Quercetin will be supplied as quercetin phytosome (sophora japonica concentrate (leaf) / phosphatidylcholine complex from Sunflower) 250 mg

Dasatinib plus Quercetin Treatment Goup

Fisetin DRUG

Fisetin will be supplied in 100 mg capsules to be administered orally

Fisetin Treatment Group

Eligibility Criteria

• Age: 60 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to provide informed consent.
• Normal postmenopausal women
• Aged ≥60 years

You may not qualify if:

• Hemoglobin A1c ≥8.0% at screening
• Subjects who are type II diabetic and on insulin
• Abnormal screening labs: Calcium \>10.1 mg/dL, Phosphorus \>4.7 mg/dL, Thyroid stimulating hormone (TSH) level \<0.3mU/L, Fasting blood glucose \>200 mg/dL.
• Presence of significant liver (total bilirubin, AST, ALT, or alkaline phosphatase \>2x upper normal limit) or kidney disease (eGFR\<30 ml/min/1.73 m2 (using the cystatin C blood levels for analysis). If any elevation were to be noted (2x the normal limit), the study participant would stop treatment and have levels re-drawn in a month, per the clinical judgement of the investigator
• Presence of a clinical diagnosis of heart failure
• Known active malignancy (including myeloma)
• Current diagnosis of malabsorption or undergoing treatment for malabsorption disease
• If any of the laboratory blood work drawn at the study visits return with lab values outside of the "normal limits" or show a significant change from a previous value, a repeat blood draw would be done before the subject is excluded.
• Gastric bypass/reduction
• Hyperthyroidism
• Acromegaly
• Cushing's syndrome
• Hypopituitarism
• Subjects with a fracture within the past six months
• Undergoing treatment with any medications that affect bone turnover, including the following:

Sponsors & Collaborators

• Sundeep Khosla, M.D.: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• Farr JN, Monroe DG, Atkinson EJ, Froemming MN, Ruan M, LeBrasseur NK, Khosla S. Characterization of Human Senescent Cell Biomarkers for Clinical Trials. Aging Cell. 2025 May;24(5):e14489. doi: 10.1111/acel.14489. Epub 2025 Jan 17.

  PMID: 39823170 DERIVED

• Farr JN, Atkinson EJ, Achenbach SJ, Volkman TL, Tweed AJ, Vos SJ, Ruan M, Sfeir J, Drake MT, Saul D, Doolittle ML, Bancos I, Yu K, Tchkonia T, LeBrasseur NK, Kirkland JL, Monroe DG, Khosla S. Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial. Nat Med. 2024 Sep;30(9):2605-2612. doi: 10.1038/s41591-024-03096-2. Epub 2024 Jul 2.

  PMID: 38956196 DERIVED

MeSH Terms

Interventions

Dasatinib; Quercetin; fisetin

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Sundeep Khosla, M.D.
• Organization: Mayo Clinic

khosla.sundeep@mayo.edu

507-255-6663

Study Officials

• Sundeep Khosla, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 18, 2020
• Study Start: June 9, 2020
• Primary Completion: June 6, 2023
• Study Completion: June 6, 2023
• Last Updated: July 22, 2024
• Results First Posted: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)