Harnessing Chronomodulation to Enhance Osteogenesis

• Status: Suspended
• Trial end date: 2023-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Chronotherapy is an emerging field in biomedicine that leverages on fine-tuning the timing of drug delivery to obtain a therapeutic effect. Dr. Tamimi and his team have successfully harnessed chronotherapy using NSAIDs to enhance bone healing in a murine fracture model. Unpublished findings revealed that mice receiving carprofen for 3 days post-fracture exclusively during activity hours exhibited superior bone healing outcomes in comparison to specimens that received the same drug during resting hours.

This is a 3-arm RCT aimed at evaluating the effect of different chronotherapeutic NSAID regimens on intraoral bone healing in humans using an extraction socket healing model in the context of an early implant placement protocol.

The primary aim is to elucidate whether there are differences in osteogenesis and in the characteristics of the newly formed bone between patients following different post-operative NSAID chronotherapeutic protocols. Secondary endpoints of interest include assessment of alveolar bone and soft tissue dimensional changes between pre- and post-extraction, implant insertion torque, serum CRP levels, wound healing index and patient-reported discomfort at different time points.

If proven beneficial, the proposed chronotherapeutic approach could be readily implemented in clinical practice as a standalone therapy or as a valuable complement to existing standard-of-care protocols, due to its simplicity, safety and cost-effectiveness.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Gustavo Avila-Ortiz DDS, MS, PhD; University of Iowa
• Collaborator: Osteology Foundation
• Treatments: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Ketoprofen

Criteria

Inclusion Criteria:

• Adult (18 years or older) males or females with an ASA status of I or II and adequate physical and mental health to undergo study-related procedures

• In need of extraction of a maxillary incisor, maxillary or mandibular canine, or maxillary or mandibular premolar and successive tooth replacement therapy according an early implant placement protocol10

• Extractions socket walls must be intact or have no more than one bony wall dehiscence or fenestration extending no more than 20% of the total bony wall height

• Subjects must have read, understood and signed the informed consent form

Exclusion Criteria:

• Acute infection associated with the tooth to be extracted or with adjacent teeth

• Known allergies or medical contraindications to any of the study-related drugs and biologic materials

• Sleeping disorders or jet lagged from a recent trip or working in night shift jobs

• History of significant heart, stomach, liver, kidney, blood, immune system disease, or other organ impairment or systemic diseases or disorders that may prevent undergoing the proposed treatment and/or may significantly affect bone healing (e.g. uncontrolled diabetes, thyroid disorders or Paget's disease)

• Current smokers or former smokers who quit less than 12 months prior to the initiation of the study

• Subjects taking any medication or supplement known to influence bone metabolism, such as IV bisphosphonates, long-term history of oral bisphosphonates or chronic intake of glucocorticoids

• Regular or within 7 days of baseline intake of any anti-inflammatory and/or analgesic drugs

• Need of oral or intravenous sedation

• Pregnant women or nursing mothers

• History of recreational drug abuse and/or heavy alcohol use

• History of lack of compliance with dental visits or unwilling to return for the required number of visits