The DENOCHARCOT Trial

February 7, 2023 updated by: Ole Lander Svendsen

Efficacy of Treatment With DENOsumab of an Acute CHARCOT Foot in Patients With Diabetes. A Multicenter, Double-blind, Randomized, Placebo-controlled Trial.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

38

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aalborg, Denmark
        • Recruiting
        • Steno Diabetes Center North
      • Aarhus, Denmark
        • Not yet recruiting
        • Steno Diabetes Center Aarhus
      • Copenhagen NV, Denmark, 2400
        • Recruiting
        • Bispebjerg Hospital
      • Gentofte, Denmark
        • Recruiting
        • Steno Diabetes Center Copenhagen
      • Hillerød, Denmark
        • Recruiting
        • Nordsjællands Hospital
      • Hvidovre, Denmark
        • Recruiting
        • Hvidovre Hospital
      • Køge, Denmark
        • Recruiting
        • Zealand University Hospital
      • Odense, Denmark
        • Not yet recruiting
        • Steno Diabetes Center Odense

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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 1. toe at the acute Charcot foot.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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
Drug: Denosumab Injection
Injections made subcutaneously per standard description
PLACEBO_COMPARATOR: Placebo treated group
Participants will receive an injection of placebo produced by the same provider as the prolia drug of equivalent volume at the same time points as the treated group
Drug: Denosumab Injection
Injections made subcutaneously per standard description

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time until remission
Time Frame: 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.
52 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Fraction of clinical healed participants at each study visit.
Time Frame: 52 weeks
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.
Time Frame: 52 weeks
52 weeks
Number of relapses (defined as need for/prescription of off- loading with cast of the Charcot foot again)
Time Frame: 52 weeks
52 weeks
Time without relapse (the time from clinical healing/remission to the relapse or to End of Trial at 12 months).
Time Frame: 52 weeks
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.
Time Frame: 52 weeks
52 weeks
Changes in BMD (lumbar spine, hip)
Time Frame: 52 weeks
52 weeks
Changes in markers of bone turnover (CTX and P1NP)
Time Frame: 52 weeks
52 weeks
Changes in markers of glycemic control (HbA1c)
Time Frame: 52 weeks
52 weeks
Incidence of Adverse Events and Serious Adverse Events
Time Frame: 52 weeks
52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ole Lander Svendsen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 1, 2020

Primary Completion (ANTICIPATED)

October 1, 2025

Study Completion (ANTICIPATED)

October 1, 2026

Study Registration Dates

First Submitted

September 7, 2020

First Submitted That Met QC Criteria

September 7, 2020

First Posted (ACTUAL)

September 14, 2020

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2023

Last Update Submitted That Met QC Criteria

February 7, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CODIF-008

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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