Charcot ArthropathyNCT02316483
Genetic Contribution to the Pathophysiology of the Charcot Foot in Qatari Patients With Diabetes
An observational study of Charcot Arthropathy and Type 2 Diabetes, run by Weill Medical College of Cornell University at 1 site in Qatar.
Trial summary
To assess the hypothesis that Charcot foot is associated with more vascular complications compared to matched diabetic patients without Charcot foot and to classify patients with Charcot foot according to the human genetic classification of the Qatari population. Read more about this study
- Who is it for?
- Ages 30 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Charcot Arthropathy, Type 2 Diabetes
- How many people
- 57 participants
- Where
- 1 siteQatar
- Study dates
- Dec 2013to Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Subjects will be recruited for the study at Hamad Medical Corporation. Most of the subjects will belong to the oupatient clinics.
Who may be able to join
- Must provide informed consent
- Must hold Qatari passport
- Males or Females ages 30 years or older to minimize the potential confounding contribution of other forms of diabetes mellitus
- In patients with Diabetes, no concomitant diseases except for micro- and macrovascular complications of diabetes (nephropathy, retinopathy, peripheral arterial disease, coronary artery disease, neuropathy) or symptoms of the metabolic syndrome (hypertension, dyslipidemia and obesity).
- Not taking any chronic medications (except of the diabetes, cardiovascular related drugs, anti-inflammatory drugs and/or any other treatment used for Charcot foot).
Who cannot join
- Other forms of diabetes (Type I, MODY, secondary diabetes)
- Active pregnancy
- Active infection or acute illness of any kind (except for Charcot foot)
- Chronic inflammation (auto-immune diseases) or infection
- Evidence of malignancy within the past 5 years
- Chronic hematological disorders known to affect HBA1C results such as hemoglobinopathies (e.g., sickle cell disease and thalassemia), increased red-cell turnover (e.g., hemolytic anemia and spherocytosis)
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- Acute or critical limb ischemia.
- Osteomyelitis
- History of recent (within 6 months) immunosuppressive treatment including corticosteroids and anti-TNF-alpha compounds.
Trial locations and contacts
1 site in 1 country.
About this study
To assess the hypothesis that Charcot foot is associated with more vascular complications compared to matched diabetic patients without Charcot foot and to classify patients with Charcot foot according to the human genetic classification of the Qatari population.
Read the detailed description
Diabetes is a serious health issue for the Qatari population since approximately 1/5 of the population has Type 2 Diabetes, which is 2-3 times higher than the world average. Although much of the clinical studies of diabetes often focused on microvascular phenotypes such as retinopathy and nephropathy, and macrovascular diseases presenting clinically as myocardial infarction, stroke, and peripheral vascular disease, other rare complications such as Charcot foot disease confer a significant burden in Qatar diabetic population, leading to decreased life quality.
Charcot foot is estimated to affect 0.8% to 8% of diabetic populations. It occurs most commonly in patients with diabetes complicated by severe peripheral neuropathy, often with coexisting sympathetic denervation, causing increased blood flow to the foot and increased bone resorption.
Uncontrolled and inappropriate inflammation leading to bone resorption and deformation has been the hallmark of diabetic Charcot foot pathophysiology. There are two major theories that provide the likely mechanism of the disease. The "neurovascular (French) theory" suggests that increased blood flow, as a result of autonomic neuropathy, can lead to bone destruction and mechanical debilitation. On the other hand, the "neurotraumatic (German) theory" argues that the loss of protective sensation leads to unperceived injury and trauma in the insensate foot. One can argue that the pathogenesis of Charcot neuro-arthropathy is most likely a combination of these processes. For unknown reasons, Charcot foot is trigged only in some susceptible individuals with diabetes.
- Conditions
- Charcot Arthropathy, Type 2 Diabetes
- Medical subject headings
- Arthropathy, Neurogenic, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group I: T2D and Charcot foot | Individuals with confirmed diagnosis of type 2 diabetes, using the American Diabetes Association guidelines and confirmed diagnosis of Charcot foot, based on clinical and radiological evidence of Charcot foot. | |
| Group II: T2D neuropathy, no charcot | Individuals with type 2 diabetes and presence of neuropathy but the absence of Charcot foot. | |
| Group III: Control, non-diabetic | Individuals without history of type 2 diabetes. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Charcot Foot's vascular complications
Assess the hypothesis that Charcot Foot is associated with more vascular complications compared to match diabetic patients without Charcot foot
Measured: 6 months
Charcot foot in monocyte epigenetics
Assess the hypothesis that Charcot foot disease reflects differences in monocyte epigenetics compared to other controls, particularly in genes involved in inflammation.
Measured: 6 months
Assess the effect of initial methylation on kidney function in patients with type 2 diabetes mellitus, weather they have or not Charcot foot disease and for whom we have baseline kidney function, in a 2-year follow-up.
Measured: 6 months
HBA1C >8.5% on total and gene-specific methylation.
Assess the effect of improving diabetes control in patients with type 2 diabetes (Charcot foot and non-charcot foot patients) and a HBA1C >8.5% on total and gene-specific methylation.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2014 (estimated)
- Study startDec 2013
- Primary completionDec 2018
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Charcot ArthropathyStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Hamad Medical Corporation, Weill Cornell Medical College in Qatar
- Responsible party
- Sponsor
- Investigators
- Charbel Abi Khalil, MD, Principal investigator, Weill Cornell Medical College in Qatar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02316483
- Sponsor's protocol ID
- 13-00031 [JIRB]
- Status last verified
- Jan 2020
- First submitted
- 9 Dec 2014
- Last updated
- 14 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: All results of the proposed studies will be published in international peer-reviewed scientific journals, presented at meetings in Qatar, the regional and international conferences, and disseminated through the local Qatari media, seminars and lectures for high school and college students. The original data will be available to interested investigators using the conventional standards of biomedical science.
Publications
Pasquier J, Ramachandran V, Abu-Qaoud MR, Thomas B, Benurwar MJ, Chidiac O, Hoarau-Vechot J, Robay A, Fakhro K, Menzies RA, Jayyousi A, Zirie M, Al Suwaidi J, Malik RA, Talal TK, Najafi-Shoushtari SH, Rafii A, Abi Khalil C. Differentially expressed circulating microRNAs in the development of acute diabetic Charcot foot. Epigenomics. 2018 Oct;10(10):1267-1278. doi: 10.2217/epi-2018-0052. Epub 2018 Jun 5.
PubMed 29869523
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Contribution to the Pathophysiology of the Charcot Foot in Qatari Patients With Diabetes
- ClinicalTrials.gov ID
- NCT02316483
- Acronym / sponsor ID
- 13-00031 [JIRB]
- Conditions
- Charcot Arthropathy, Type 2 Diabetes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Hamad Medical Corporation, Weill Cornell Medical College in Qatar
- Study start
- Dec 2013
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 15 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the hypothesis that Charcot foot is associated with more vascular complications compared to matched diabetic patients without Charcot foot and to classify patients with Charcot foot according to the human genetic classification of the Qatari population.
Detailed description
Diabetes is a serious health issue for the Qatari population since approximately 1/5 of the population has Type 2 Diabetes, which is 2-3 times higher than the world average. Although much of the clinical studies of diabetes often focused on microvascular phenotypes such as retinopathy and nephropathy, and macrovascular diseases presenting clinically as myocardial infarction, stroke, and peripheral vascular disease, other rare complications such as Charcot foot disease confer a significant burden in Qatar diabetic population, leading to decreased life quality.
Charcot foot is estimated to affect 0.8% to 8% of diabetic populations. It occurs most commonly in patients with diabetes complicated by severe peripheral neuropathy, often with coexisting sympathetic denervation, causing increased blood flow to the foot and increased bone resorption.
Uncontrolled and inappropriate inflammation leading to bone resorption and deformation has been the hallmark of diabetic Charcot foot pathophysiology. There are two major theories that provide the likely mechanism of the disease. The "neurovascular (French) theory" suggests that increased blood flow, as a result of autonomic neuropathy, can lead to bone destruction and mechanical debilitation. On the other hand, the "neurotraumatic (German) theory" argues that the loss of protective sensation leads to unperceived injury and trauma in the insensate foot. One can argue that the pathogenesis of Charcot neuro-arthropathy is most likely a combination of these processes. For unknown reasons, Charcot foot is trigged only in some susceptible individuals with diabetes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group I: T2D and Charcot foot | – | –Individuals with confirmed diagnosis of type 2 diabetes, using the American Diabetes Association guidelines and confirmed diagnosis of Charcot foot, based on clinical and radiological evidence of Charcot foot. |
| Group II: T2D neuropathy, no charcot | – | –Individuals with type 2 diabetes and presence of neuropathy but the absence of Charcot foot. |
| Group III: Control, non-diabetic | – | –Individuals without history of type 2 diabetes. |
Who may qualify
- Ages
- 30 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects will be recruited for the study at Hamad Medical Corporation. Most of the subjects will belong to the oupatient clinics.
Key inclusion criteria (5 listed)
- Must provide informed consent
- Must hold Qatari passport
- Males or Females ages 30 years or older to minimize the potential confounding contribution of other forms of diabetes mellitus
- In patients with Diabetes, no concomitant diseases except for micro- and macrovascular complications of diabetes (nephropathy, retinopathy, peripheral arterial disease, coronary artery disease, neuropathy) or symptoms of the metabolic syndrome (hypertension, dyslipidemia and obesity).
- Not taking any chronic medications (except of the diabetes, cardiovascular related drugs, anti-inflammatory drugs and/or any other treatment used for Charcot foot).
Key exclusion criteria (9 listed)
- Other forms of diabetes (Type I, MODY, secondary diabetes)
- Active pregnancy
- Active infection or acute illness of any kind (except for Charcot foot)
- Chronic inflammation (auto-immune diseases) or infection
- Evidence of malignancy within the past 5 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Charcot Foot's vascular complications
Time frame: 6 months
Assess the hypothesis that Charcot Foot is associated with more vascular complications compared to match diabetic patients without Charcot foot
Charcot foot in monocyte epigenetics
Time frame: 6 months
Assess the hypothesis that Charcot foot disease reflects differences in monocyte epigenetics compared to other controls, particularly in genes involved in inflammation.
Assess the effect of initial methylation on kidney function in patients with type 2 diabetes mellitus, weather they have or not Charcot foot disease and for whom we have baseline kidney function, in a 2-year follow-up.
Time frame: 6 months
HBA1C >8.5% on total and gene-specific methylation.
Time frame: 6 months
Assess the effect of improving diabetes control in patients with type 2 diabetes (Charcot foot and non-charcot foot patients) and a HBA1C >8.5% on total and gene-specific methylation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2020.
- Derived from this study: PubMed 29869523Pasquier J, Ramachandran V, Abu-Qaoud MR, Thomas B, Benurwar MJ, Chidiac O, Hoarau-Vechot J, Robay A, Fakhro K, Menzies RA, Jayyousi A, Zirie M, Al Suwaidi J, Malik RA, Talal TK, Najafi-Shoushtari SH, Rafii A, Abi Khalil C. Differentially expressed circulating microRNAs in the development of acute diabetic Charcot foot. Epigenomics. 2018 Oct;10(10):1267-1278. doi: 10.2217/epi-2018-0052. Epub 2018 Jun 5.
- Individual participant dataSharing planned: Yes. All results of the proposed studies will be published in international peer-reviewed scientific journals, presented at meetings in Qatar, the regional and international conferences, and disseminated through the local Qatari media, seminars and lectures for high school and college students. The original data will be available to interested investigators using the conventional standards of biomedical science.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charbel Abi Khalil, MD principal investigator
Weill Cornell Medical College in Qatar
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Charcot Arthropathy and Type 2 Diabetes, run by Weill Medical College of Cornell University at 1 site in Qatar.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Qatar. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Charcot Foot's vascular complications (time frame: 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02316483, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2020.