Efficacy of Treatment With DENOsumab of an Acute CHARCOT Foot in Patients With Diabetes. A Multicenter, Double-blind, Randomized, Placebo-controlled Trial.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 38
- 试验地点
- 8
- 主要终点
- Time until remission
研究概览
简要总结
The aim of the present trial is to assess the efficacy of treatment of acute Charcot foot in diabetes patients with Prolia® on clinical relevant Outcomes in a randomized, double blind, placebo-controlled trial.
详细描述
After giving informed consent and being enrolled, patients will be randomized to one of two group given either Denosumab treatment or injection with placebo. The patients will then undergo a 52 week follow up with regular controls to asses if clinical signs of Charcot is in remission, which will be verified using relevant radiological modalities. Upon final visit the patients will be examined using radiology, blood samples, biothesiometry and objective examinations, following up on the same examinations being made upon inclusion.
Primary outcome will be time until full remission of the Charcot foot defined as clinical healing (The acute Charcot foot is clinically healed when the temperature difference at the site maximum temperature on the affected Charcot foot is < 2 degrees Celsius compared to the similar site on the contra-lateral foot, measured using an infrared thermometer, and edema and redness of the skin has subsided) followed up by radiological signs of healing.
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, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-80 years
- •Type 1 or type 2 diabetes (diagnosed diabetes for more than 3 months)
- •Diagnosed with acute Charcot foot defined as a unilateral red, swollen and warm foot, with a difference of skin temperature of more than 2 °C compared with the unaffected foot and with sign of Charcot on either x-rays of the foot, MRI, bone scintigram or PET/CT.
- •Peripheral neuropathy: Previously diagnosed and/or biothesiometri: > 25 V or lack of sensation of 10 grams monofilament on
- •toe at the acute Charcot foot.
排除标准
- •Duration of the acute Charcot foot for more than 3 months (at the screening visit).
- •Existing foot ulcer on the affected foot
- •Previous acute or chronic Charcot of the affected foot
- •Planned surgery on the acute Charcot foot
- •Infection (cellulitis or osteomyelitis) of the affected foot (clinically and/or radiologically proven)
- •Previous midfoot or proximal to mid foot amputation of the affected foot
- •Hypocalcemia (Serum Calcium <2.1 mmol/L or Calcium ion < 1.12 mmol/L)
- •Vitamin D deficiency (Serum 25-hydroxyvitamin D < 50 nmol/L)
- •Renal failure (serum creatinine >200 mmol/L or eGFR < 30 ml/min).
- •Treatment with Denosumab within the last 12 months. • Have a known hypersensitivity to Denosumab • History of osteonecrosis of the jaw.
- •Poor oral hygiene, which is defined as within 3 months of a tooth extraction, dental implants or mandibular surgery
- •Planned mandibular surgery or dental implants within the next 12 months.
- •Prior non-traumatic vertebral fracture
- •Treatment with medication known to affect bones within the last 12 months (such as bisphosphonates, Forsteo®, calcitonin, Protelos®, selective estrogen receptor modulators, glucocorticoids and sex hormones)
- •Active or chronic liver disease *Chronic liver disease is defined as clinical history of decompensated chronic liver disease (ascites, encephalopathy or variceal bleeding) *Acute Liver disease is defined as an INR of > 1.5 (in the absence of the use of Warfarin) and AST and ALT > 2 x ULN
- •History of inflammatory arthropathies (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, autoimmune arthropathy)
- •Pre-existing medical condition judged to preclude safe participation in the study
- •Current treatment with cytotoxic drugs or with systemically administered glucocorticoids
- •Abuse of alcohol or drugs, or presence of any condition that in the Investigators opinion may lead to poor adherence to study protocol
- •Pregnancy, breast feeding or planning pregnancy or not using adequate contraceptive methods. The following contraceptive products are considered to be safe: Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections).
- •Likely inability to comply with the visits because of planned activity
- •Use of any investigational product with the last month.
- •Use of any drug or any other reason which in the Investigator's opinion could interfere with the outcome of the treatment of the acute Charcot foot.
- •Cancer, or any clinically significant disease or disorder, except for conditions associated to the diabetes, which in the Investigator's opinion could interfere with the results of the trial
研究组 & 干预措施
Denosumab treated group
Participants will receive a 60 mg subcutaneous injection of Prolia upon randomization and on week 28 after the first injection provided remission of the Charcot foot has not been achieved by then
干预措施: Denosumab Injection (Drug)
Placebo treated group
Participants will receive an injection of placebo (saline) instead of Prolia
干预措施: Denosumab Injection (Drug)
结局指标
主要结局
Time until remission
时间窗: 52 weeks
Time from first injection of IP until the time point where the acute Charcot foot is clinically healed/in remission, ie. the temperature difference at the site maximum temperature on the affected Charcot foot is \< 2 degrees Celsius compared to the similar site on the contra-lateral foot, measured using an infrared thermometer, and edema and redness of the skin has subsided - at two subsequent visits 4 weeks apart. The off-loading regime will be continued until the second visit. The first of the two visits is the timepoint of healing of the acute Charcot foot.
次要结局
- Changes in BMD (lumbar spine, hip)(52 weeks)
- Changes in markers of bone turnover (CTX and P1NP)(52 weeks)
- Fraction of clinical healed participants at each study visit.(52 weeks)
- Time without relapse (the time from clinical healing/remission to the relapse or to End of Trial at 12 months).(52 weeks)
- Number of patients with development of complications to the acute Charcot foot, as well as number of development of foot ulcer, deformity, need for special footwear or surgery and fractures of bones in the foot, respectively.(52 weeks)
- Changes in markers of glycemic control (HbA1c)(52 weeks)
- Fraction of healing on X-rays and MRI (or PET/CT or Scintigram) at the time of clinical healing and at the End of trial.(52 weeks)
- Number of relapses (defined as need for/prescription of off- loading with cast of the Charcot foot again)(52 weeks)
- Incidence of Adverse Events and Serious Adverse Events(52 weeks)
研究者
Ole Lander Svendsen
Professor
Bispebjerg Hospital