The DENOCHARCOT Trial

NCT04547348 | Recruiting Phase 3 DMC

• 1 other identifier: CODIF-008
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Charcot Foot; Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Time until remission

  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 Outcomes (9)

• Fraction of clinical healed participants at each study visit.

  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

• 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

Study Arms (2)

Denosumab treated group

EXPERIMENTAL

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

Placebo treated group

PLACEBO COMPARATOR

Participants will receive an injection of placebo (saline) instead of Prolia

Drug: Denosumab Injection

Interventions

Denosumab Injection DRUG

Injections made subcutaneously per standard description

Denosumab treated group; Placebo treated group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ole Lander Svendsen: lead

Study Sites (8)

Steno Diabetes Center North

Aalborg, Denmark

RECRUITING

Steno Diabetes Center Aarhus

Aarhus, Denmark

RECRUITING

Bispebjerg Hospital

Copenhagen NV, 2400, Denmark

RECRUITING

Steno Diabetes Center Copenhagen

Gentofte Municipality, Denmark

RECRUITING

Nordsjællands Hospital

Hillerød, Denmark

RECRUITING

Hvidovre hospital

Hvidovre, Denmark

RECRUITING

Zealand University Hospital

Køge, Denmark

RECRUITING

Steno Diabetes Center Odense

Odense, Denmark

RECRUITING

Related Publications (11)

• Jeffcoate WJ. Charcot foot syndrome. Diabet Med. 2015 Jun;32(6):760-70. doi: 10.1111/dme.12754. Epub 2015 Apr 15.

  PMID: 25818542 BACKGROUND

• Christensen TM, Gade-Rasmussen B, Pedersen LW, Hommel E, Holstein PE, Svendsen OL. Duration of off-loading and recurrence rate in Charcot osteo-arthropathy treated with less restrictive regimen with removable walker. J Diabetes Complications. 2012 Sep-Oct;26(5):430-4. doi: 10.1016/j.jdiacomp.2012.05.006. Epub 2012 Jun 12.

  PMID: 22699112 BACKGROUND

• Pitocco D, Ruotolo V, Caputo S, Mancini L, Collina CM, Manto A, Caradonna P, Ghirlanda G. Six-month treatment with alendronate in acute Charcot neuroarthropathy: a randomized controlled trial. Diabetes Care. 2005 May;28(5):1214-5. doi: 10.2337/diacare.28.5.1214. No abstract available.

  PMID: 15855594 BACKGROUND

• Anderson JJ, Woelffer KE, Holtzman JJ, Jacobs AM. Bisphosphonates for the treatment of Charcot neuroarthropathy. J Foot Ankle Surg. 2004 Sep-Oct;43(5):285-9. doi: 10.1053/j.jfas.2004.07.005.

  PMID: 15480402 BACKGROUND

• Jude EB, Selby PL, Burgess J, Lilleystone P, Mawer EB, Page SR, Donohoe M, Foster AV, Edmonds ME, Boulton AJ. Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial. Diabetologia. 2001 Nov;44(11):2032-7. doi: 10.1007/s001250100008.

  PMID: 11719835 BACKGROUND

• Bem R, Jirkovska A, Fejfarova V, Skibova J, Jude EB. Intranasal calcitonin in the treatment of acute Charcot neuroosteoarthropathy: a randomized controlled trial. Diabetes Care. 2006 Jun;29(6):1392-4. doi: 10.2337/dc06-0376. No abstract available.

  PMID: 16732029 BACKGROUND

• Pakarinen TK, Laine HJ, Maenpaa H, Mattila P, Lahtela J. The effect of zoledronic acid on the clinical resolution of Charcot neuroarthropathy: a pilot randomized controlled trial. Diabetes Care. 2011 Jul;34(7):1514-6. doi: 10.2337/dc11-0396. Epub 2011 May 18.

  PMID: 21593295 BACKGROUND

• Petrova NL, Dew TK, Musto RL, Sherwood RA, Bates M, Moniz CF, Edmonds ME. Inflammatory and bone turnover markers in a cross-sectional and prospective study of acute Charcot osteoarthropathy. Diabet Med. 2015 Feb;32(2):267-73. doi: 10.1111/dme.12590. Epub 2014 Oct 17.

  PMID: 25251588 BACKGROUND

• Jansen RB, Christensen TM, Bulow J, Rordam L, Jorgensen NR, Svendsen OL. Markers of Local Inflammation and Bone Resorption in the Acute Diabetic Charcot Foot. J Diabetes Res. 2018 Aug 2;2018:5647981. doi: 10.1155/2018/5647981. eCollection 2018.

  PMID: 30155488 BACKGROUND

• Busch-Westbroek TE, Delpeut K, Balm R, Bus SA, Schepers T, Peters EJ, Smithuis FF, Maas M, Nieuwdorp M. Effect of Single Dose of RANKL Antibody Treatment on Acute Charcot Neuro-osteoarthropathy of the Foot. Diabetes Care. 2018 Mar;41(3):e21-e22. doi: 10.2337/dc17-1517. Epub 2017 Dec 22. No abstract available.

  PMID: 29273577 BACKGROUND

• Tsourdi E, Langdahl B, Cohen-Solal M, Aubry-Rozier B, Eriksen EF, Guanabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Zillikens MC. Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS. Bone. 2017 Dec;105:11-17. doi: 10.1016/j.bone.2017.08.003. Epub 2017 Aug 5.

  PMID: 28789921 BACKGROUND

Related Links

• Prolia product summary
• Xgeva product summary

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ole Lander Svendsen, MD

  Region Hovedstadens Apotek

  STUDY CHAIR

Central Study Contacts

Ole Lander Svendsen, MD

CONTACT

+4521490547; Ole.Lander.Svendsen@regionh.dk

Michael Zaucha Sørensen, MD

CONTACT

+4526836584; mzs@dadlnet.dk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: September 14, 2020
• Study Start: November 1, 2020
• Primary Completion: October 1, 2025
• Study Completion (Estimated): October 1, 2026
• Last Updated: August 7, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (8)