Harnessing Chronomodulation to Enhance Osteogenesis - A Pilot Randomized Controlled Trial -
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 主要终点
- proportion (%) of mineralized tissue
研究概览
简要总结
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 Unpublished findings revealed that mice receiving carprofen for 3 days post-fracture exclusively during activity hours exhibited superior bone healing outcomes in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.
详细描述
Enrolled subjects will be randomly assigned to one of three groups (n=12 per group):
Group A (Test) - Tooth extraction and intake of an NSAID (i.e. Ketoprofen ER 50 mg) at 8 AM and a non-NSAID (i.e. Acetaminophen / Paracetamol 500 mg) at 2 PM and 8 PM for a 3-day period, starting at 2 PM on the day of the extraction.
Group B (Control 1) - Tooth extraction and intake of an NSAID (i.e. Ketoprofen ER 50 mg) at 8 PM and a non-NSAID (i.e. Acetaminophen / Paracetamol 500 mg) at 8 AM and 2 PM for a 3-day period, starting at 2 PM on the day of the extraction.
Group C (Control 2) - Tooth extraction and intake of a non-NSAID (i.e. Acetaminophen / Paracetamol 500 mg) at 8AM, 2 PM and 8 PM for a 3-day period, starting at 2 PM on the day of the extraction.
VISIT 1 - Screening Referred or self-referred subjects that appear to meet all the eligibility criteria upon phone pre-screening will be invited to an in-person screening visit at the UICOD. The study purpose, duration, potential risks and expected benefits will be explained in detail to the subjects, as part of the consenting process. All screened subjects will be provided with hard copies of the study timeline and the signed consent form. Upon medical and dental history review, as well as site-specific clinical and radiographic evaluation, eligible subjects interested in participating in the study will be scheduled for Visit 2. Intraoral photographs of the site of interest will be taken. Additionally, a cone-beam computed tomography (CBCT) scan will be obtained and interpreted to evaluate the study site, prior to the baseline intervention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Participants, Surgeon and Assessors collecting the data and conducting the appropriate statistical analyses for all outcomes in the study will be blinded.
All surgical procedures will be scheduled between 8 and 10 AM and performed by the same blinded clinician to maintain a consistent therapeutic approach for all subjects.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
结局指标
主要结局
proportion (%) of mineralized tissue
时间窗: 6 weeks after extraction
proportion (%) of mineralized tissue present in the bone core samples obtained at the time of implant placement, approximately 6 weeks after tooth extraction. This will be evaluated via histomorphometric analysis.
次要结局
- µCT analysis(6 weeks post-extraction)
- Alveolar ridge contour variations(Baseline to 6 weeks post-extraction)
- Implant insertion torque(6 weeks post-extraction)
- Alveolar bone variations(Baseline to 6 weeks post-extraction)
- Serum CRP(6 weeks post-extraction)
- Wound Healing Index (WHI)(8 weeks post-extraction)
- Patient Reported Outcome Measures (PROMS)(Day 7 post-extraction)
研究者
Satheesh Elangovan
Principal Investigator
University of Iowa