Senolytics to Improve Osteoporosis Therapy

NCT06018467 | Active Not Recruiting Phase 2 DMC

• 3 other identifiers: EU CT: 2022-502076-23-002022-502076-23-00NNF21OC0067839
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This randomised clinical trial aims to study osteoporosis as a disease of accelerated skeletal aging caused by the accumulation of senescent cells within the skeleton and investigate the effects and safety of senolytics and antioxidant therapy on bone.

Conditions

Osteopenia, Osteoporosis; Age-related Bone Loss

Keywords

Age related bone loss; Cellular senescence; senolytic; senolytics; Dasatinib; Quercetin; NR; Nicoinamide riboside

Outcome Measures

Primary Outcomes (1)

• Bone resorption marker CTX

  Change in circulating marker of bone resorption C-terminal telopeptide of type I collagen (CTX) at 21 weeks.

  Baseline, week 5, week 13, week 21

Secondary Outcomes (2)

• Bone resorption marker TRAcP

  Baseline, week 5, week 13, week 21

• Bone formation markers (PINP, osteocalcin, and bone alkaline phosphatase)

  Baseline, week 5, week 13, week 21

Study Arms (3)

Dasatinib plus Quercetin (DQ)

EXPERIMENTAL

Study participants will receive a combination of 100 mg/d dasatinib (oral) for two consecutive days and 1.250 mg/d quercetin (oral) for three consecutive days followed by 25 days without treatment, with treatment being repeated every 4 weeks for a total of 20 weeks (i.e., 5 times)

Drug: Dasatinib 100 Mg Oral Tablet; Dietary Supplement: Quercetin 1.250 mg (oral)

Nicotinamide Riboside (NR)

EXPERIMENTAL

The participants will receive treatment with 1g Nicotinamide Riboside (oral) daily for 20 weeks

Dietary Supplement: Nicotinamide Riboside 1g (oral)

Control

NO INTERVENTION

The participants in the Control group, will not receive any treatment for 20 weeks.

Interventions

Dasatinib 100 Mg Oral Tablet DRUG

Dasatinib tablets in blister packs of 10 tablets, from either: "Sandoz", "STADA Nordic", "Zentiva" or "Bristol-Myers Squibb"

Also known as: Sprycel

Dasatinib plus Quercetin (DQ)

Quercetin 1.250 mg (oral) DIETARY_SUPPLEMENT

five 200mg Quercetin Phytosome capsules, from Thorne

Also known as: Quercetin Phytosome

Dasatinib plus Quercetin (DQ)

Nicotinamide Riboside 1g (oral) DIETARY_SUPPLEMENT

four 250mg Nicotinamide Riboside Capsules, from Elysium Health

Also known as: NR

Nicotinamide Riboside (NR)

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women (menopause \> 5 years and FSH and LH in the postmenopausal range) aged 60-90 years with increased fracture risk according to WHO 10 years absolute Fracture Risk Assessment Tool (FRAX)
• Osteopenia (ICD10 DM858A) based on a T-score ≤ -1 to -2.5 at the total hip/femoral neck, or lumbar spine, with or without a fragility fracture at any time (excluding hip and vertebral fractures within the last 2 years)
• osteoporosis (ICD10 DM819) based on a T-score between ≥-3 and ≤ -2.5, which includes candidates suitable for conventional osteoporosis therapies, but who prefer to participate in the trial, despite being candidates for conventional osteoporosis therapy, or candidates which cannot be treated with conventional therapies due to contraindications
• Ability to provide informed consent

You may not qualify if:

• DXA of hip or spine not possible e.g., due to a prosthesis
• Inability to provide fasting blood samples
• Primary hyperparathyroidism
• Vitamin D deficiency (\<50 nM) (re-test after substitution acceptable)
• Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, chronic kidney disease defined as eGFR \<30 or liver dysfunction, rheumatism, celiac disease/malabsorption, hypogonadism, severe COPD, hypopituitarism, Cushing's disease, uncontrolled diabetes (HbA1c \> 58 mmol/mol).
• Antiresorptive or bone anabolic drugs for the last 2 years (5 years if treated with zoledronic acid)
• Concomitant treatments known to influence bone metabolism e.g., glucocorticoids (systemic treatments), anabolic steroids, etc.
• Subjects taking the following other drugs if they cannot be held for at least 2 days before and during administration of D+Q: digoxin, lithium, all statins, repaglidine, bosentan, gemfibrozil, olmesartan, enalapril, valsartan, methotrexate, corticosteroids, eluxadoline, eltrombopag, nitroglycerin, pioglitazone, glyburide, enzalutamide, ezetimibe, colchicine, imatinib, cyclosporine, tacrolimus, sirolimus, carbamazepine, flecainide, phenytoin, phenobarbital, rifampicin, theophylline, warfarin, heparin, clopidogrel, celecoxib, desipramine, thioridazine, venlafaxine, tizanidine, atomoxetine, voriconazole, citalopram, diazepam, escitalopram, propranolol, clozapine, cyclobenzaprine, mexiletine, olanzapine, ondansetron
• Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4 (e.g., cyclosporine, tacrolimus or sirolimus). If antifungals are necessary from an infectious disease perspective, then they will be allowed only if the levels are therapeutic.
• Subjects taking proton pump inhibitors and unwilling to discontinue therapy for two days before and during the study drug dosing periods.
• Anti-arrhythmic medications known to cause QTc prolongation
• Tyrosine kinase inhibitor therapy
• Subjects with an abnormal Complete Blood Count (clinically insignificant changes would be acceptable based on the judgement of the investigators)
• Subjects on antiplatelet agents (Clopidogrel; Dipyridamole + ASA; ASA, Ticagrelor; Prasugrel; Ticlopidine or other) who are unable or unwilling to reduce or hold therapy prior to and during the study drug dosing periods and collection of bone biopsies. Subjects may continue their previous regimen between study drug dosing periods.
• Known allergy to dasatinib, quercetin, or nicotinamide riboside

Sponsors & Collaborators

• Odense University Hospital: lead
• Odense Patient Data Explorative Network: collaborator
• The Novo Nordisk Foundation Center for Basic Metabolic Research: collaborator

Study Sites (1)

Odense University Hospital

Odense, 5000, Denmark

Location

MeSH Terms

Conditions

Bone Diseases, Metabolic; Osteoporosis

Interventions

Dasatinib; Tablets; Quercetin; nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Moustapha Kassem, DMSc, PhD

  Head of Research, Department of Endocrinology, Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2023
• First Posted: August 30, 2023
• Study Start: September 6, 2023
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)