Defining Outcome Measures for Acute Charcot Neuroarthropathy in Diabetes and Their Use in Assessing Clinical Management (CADOM)

A Randomised Feasibility Trial to Define Outcome Measures for Acute Charcot Neuroarthropathy in Diabetes and Their Use in Assessing Clinical Management (CADOM)

The aim of this study is to explore the use of serial magnetic resonance imaging (MRI) in an attempt to reduce the duration of immobilisation of the foot and thereby reduce the morbidity associated with its routine management and reduce costs. The project will have two components: a feasibility study and embedded within this a qualitative study of the patient's perspective of the experience of being diagnosed with Charcot neuroarthropathy (CN) and undergoing treatment.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Radiation: Serial MRIs

Detailed Description

The aim of the study is to assess the feasibility of using serial magnetic resonance imaging (MRI) to reduce treatment times in Charcot in people with diabetes.

Charcot is a devastating complication for people who develop it. There are over 4000 new cases of Charcot diagnosed every year. If the inflammation goes on for long enough it can cause fractures and dislocations within the foot, which left untreated can lead to foot deformity and complications such as ulcerations.

A diagnosis of Charcot has been shown to reduce people's quality of life. People who have had this condition die on average 14years younger than the general population. Every year about 50-100 people who have been diagnosed with Charcot neuroarthropathy undergo an amputation of their leg.

Charcot is treated by wearing a non-removable cast or boot. No-one knows how long this treatment should last, some recommend 6 months, others more than a year. Early treatment has been shown to lead to fewer complications.

There is some information from small studies that repeated assessment with MRI may prove useful in helping clinicians decide when to stop treatment, and it may decrease treatment times.

This study will be a feasibility study involving 60 people. Patients will be recruited from hospital run Diabetic Foot Clinics. Patients will be randomised to either receive MRI at baseline 3,6,9 and 12 months or to receive current usual care; repeated foot temperature measurements and x-rays. If the study results indicate the study is feasible to do, the information will be used to design a much larger study.

Some patients will also be asked to participate in an interview at the end of the study, to gain insights into their experience of having Charcot and involvement in the study.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UY
      • Norfolk & Norwich University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants who are willing and have capacity to give informed consent
• People with diabetes as diagnosed by the WHO criteria
• Age 18 years or over
• New or suspected diagnosis of acute CN (no previous incidence of acute CN within the last 6 months on the same foot) treated with off-loading
• Understand written and verbal instructions in English

Exclusion Criteria:

• People who have received a transplant and others receiving immunosuppressant therapy or using long term oral glucocorticoids other than in the routine management of glucocorticoid deficiency. Participants on a low doses of oral glucocorticoids (<10mgs for ≤7 days) are eligible to participate in the study.
• Participation in another intervention study on active CN
• Contra-indication for MRI
• Treatment for previous suspected CN on the same foot in the last 6 months
• Suspected or confirmed bilateral active CN at presentation
• Active osteomyelitis at randomisation
• Previous contralateral major amputation
• Inability to have an MRI scan
• Patients receiving palliative care

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (Intervention - Standard Care and Serial MRIs); Immobilisation discontinued on the basis of MRI defined disease resolution at 3, 6, 9 or 12 months. In the intervention arm participants will receive additional MRIs at 3, 6, 9 and 12 months. Patients randomised to serial MRI will not undergo further MRI once remission has been diagnosed i.e. if remission is diagnosed at 6 months the MRI at 9 and 12 months will not occur.	Radiation: Serial MRIs; Serial use of MRI at 3, 6, 9 and 12 months to identify disease resolution and thus discontinuation of immobilisation plus standard care.; Other Names: Serial use of MRI at 3, 6, 9 and 12 months
No Intervention: Arm B (Control - Standard Care and one additional MRI); Immobilisation discontinued on the basis of clinical remission determined by skin temperature measurement and MRI. In the standard care arm participants will receive one additional MRI when the temperature measurements, X-ray and/or signs and symptoms indicate to the clinical team that the foot is in remission. A temperature difference of ≤ 2ºC which is maintained or improves on two separate consecutive occasions for a period of ≥4weeks will be the indicator to arrange the second MRI, to confirm the diagnosis of remission. If participants in either arm of the trial have not reached remission at the end of the 12 month active phase of the study they will exit the study. Ongoing standard care will be provided by their clinical team.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients who meet eligibility criteria.	Feasibility outcome.	through study completion, an average of 4 years
The number of eligible patients recruited.	Feasibility outcome.	through study completion, an average of 4 years
The number of participants in which an alternative diagnosis of the foot disease is made during the intervention phase of the trial.	Feasibility outcome.	through study completion, an average of 4 years
The proportion of patients that withdraw or are lost to follow up.	Feasibility outcome. The term 'withdrawal' encompasses two potential scenarios; withdrawal due to loss of consent or withdrawal due to death.	through study completion, an average of 4 years
Quality of life and resource data collection - Sf12.	Feasibility outcome. Feasibility of quality of life and resource data collection will be assessed for data completeness and consistency using Sf12.	through study completion, an average of 4 years
Quality of life and resource data collection - EQ5D.	Feasibility outcome. Feasibility of quality of life and resource data collection will be assessed for data completeness and consistency using EQ5D.	through study completion, an average of 4 years
Quality of life and resource data collection - HADS.	Feasibility outcome. Feasibility of quality of life and resource data collection will be assessed for data completeness and consistency using HADS.	through study completion, an average of 4 years
Quality of life and resource data collection - VAS.	Feasibility outcome. Feasibility of quality of life and resource data collection will be assessed for data completeness and consistency using VAS.	through study completion, an average of 4 years
Quality of life and resource data collection - patient diary.	Feasibility outcome. Feasibility of quality of life and resource data collection will be assessed for data completeness and consistency using patient diary.	through study completion, an average of 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days with immobilisation	Days with immobilisation measured at the end study.	through study completion, an average of 4 years
Progression of foot deformity as documented by measuring radiological foot alignment angles.	All x-rays will be taken in a weight bearing position with standard views as per WPD. Comparison from baseline, diagnosis of remission, and six months after remission.	Six months after remission.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain in the foot, ankle or leg measured, using the Numeric Pain Rating Scale.	Patient Reported Outcome Measures - VAS - Visual Analogue Scale. Minimum value 0 (no pain at all) Maximum 100 (pain as bad as it could possibly be)	At randomisation, and three monthly until patient is in remission. Also collected at 1 month and 6 months post remission
Health related quality of life.	Patient Reported Outcome Measures. Health related quality of life assessed by the Medical Outcomes Short-Form Health Questionnaire (SF12) - Sf12 - Short form 12 health related quality of life questionnaire. Not a scale.	At randomisation, and three monthly until patient is in remission. Also collected at 1 month and 6 months post remission
Psychological health status.	Patient Reported Outcome Measures. Psychological health status measured using the Hospital Anxiety and Depression Scale (HADs) - HADS - Hospital Anxiety and Depression Scale. Participant selects statements that best reflect their feelings. Not a numbered scale.	At randomisation, and three monthly until patient is in remission. Also collected at 1 month and 6 months post remission
EQ-5D-5L	Patient Reported Outcome Measures - EQ-5D-5L - health related quality of life questions across five dimensions. One scale used for participant to reflect how they feel their health is on the day of completion. Scale is 0-100, 0 is the worst health imaginable and 100 is the best health imaginable	At randomisation, and three monthly until patient is in remission. Also collected at 1 month and 6 months post remission
Economic Evaluation - Reported through a patient diary	Patient Reported Outcome Measures. Collecting resource use and quality of life data, to inform the design of the health economics component of a future definitive trial - Participant asked if working and if this has changed because of their condition. Also asked to indicate if there are any costs associated with attendance at medical appointments (travel and/or parking).	At randomisation, and three monthly until patient is in remission. Also collected at 1 month and 6 months post remission

Collaborators and Investigators

• Sponsor: Norfolk and Norwich University Hospitals NHS Foundation Trust
• Collaborators: University of East Anglia
• Investigators: Study Chair: Catherine Gooday, Clinical Research and Trials Unit (Norfolk & Norwich University Hospital, UK)

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2017
• Primary Completion (Actual): November 30, 2019
• Study Completion (Actual): May 4, 2021

Study Registration Dates

• First Submitted: April 29, 2021
• First Submitted That Met QC Criteria: October 29, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

• Last Update Posted (Actual): November 3, 2021
• Last Update Submitted That Met QC Criteria: October 29, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Charcot neuroarthropathy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus
• Other Study ID Numbers: 222668 (15-01-16); ICA-CDRF-2015-01-050 (Other Grant/Funding Number: NIHR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No