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Microcirculation and Bone Metabolism in Patients With Type 2 Diabetes Mellitus and Charcot Foot - A Pilot Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02435329
Recruitment Status : Completed
First Posted : May 6, 2015
Last Update Posted : September 16, 2019
Sponsor:
Collaborator:
Manchester Metropolitan University
Information provided by (Responsible Party):
Tameside General Hospital

Brief Summary:

This study is part of a research project for a University MD Program. This is an observational study aimed at comparing the differences in bone metabolism and microcirculation in patients with type 2 diabetes mellitus (with and without diabetic neuropathy and Charcot foot) with healthy subjects.

Diabetes is gradually becoming a global epidemic along with its associated complications. Diabetes can affect several systems in our body particularly the eyes, nerves and the kidneys. The damaging effects occur at the level of the small blood vessels (microcirculation) that supply these vital structures. Normally, the inner lining of these blood vessels (endothelium) plays a very important role in maintaining adequate blood flow. The endothelium releases a chemical substance called nitric oxide, which relaxes these small blood vessels thereby ensuring sufficient blood supply to these key structures. Nitric oxide also prevents blockage of these vessels. Any form of metabolic stress like hyperglycaemia (raised blood sugar as seen in diabetes) can cause abnormal changes in the normal behaviour of the endothelium (endothelial dysfunction). Therefore hyperglycaemia promotes endothelial dysfunction by lowering nitric oxide levels, which may lead to diabetic complications like diabetic retinopathy (eye damage), nephropathy (kidney damage) or neuropathy (nerve damage).

In addition, patients with diabetes also suffer from osteoporosis (thinning of bones). Osteoporosis is a bone disorder characterised by a reduction in bone mineral content leading to an increased risk of developing fractures. The increased risk of fractures in patients with type 2 diabetes is attributed to poor bone quality resulting from the harmful effects of high blood glucose. Studies have also shown that nitric oxide has a bone protective effect as demonstrated by its ability to prevent bone fragmentation and improve bone strength.

Study of markers of endothelial function and bone metabolism will facilitate a better understanding about the origin of diabetic complications. This will aid in the development of novel therapeutic agents that target the harmful triggers in diabetes and eventually may prevent and retard the onset of the debilitating diabetic complications.


Condition or disease Intervention/treatment
Diabetic Angiopathies Bone Diseases, Metabolic Other: Baseline comparison of microcirculation and bone metabolism

  Show Detailed Description

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Study Type : Observational
Actual Enrollment : 31 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Bone Metabolism and Endothelial Function in Patients With Type 2 Diabetes Mellitus and Charcot Foot - an Observational Comparative Study
Actual Study Start Date : June 2015
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Foot Health

Group/Cohort Intervention/treatment
Healthy volunteers

10 healthy volunteers

  • Anthropometric measures: Height, weight, BMI, waist circumference
  • Vital parameters: supine and standing blood pressure, pulse, respiratory rate and temperature
  • Laboratory assessment that includes markers of endothelial activation, inflammation and bone metabolism.
  • Assessment of skin microcirculation with Laser Doppler Iontophoresis
  • Assessment of calcaneal bone mineral density (BMD) with Bone Sonometer (ultrasound)
  • Advanced glycation end-products will be assessed by an AGE reader which uses the technique of skin autofluorescence
Other: Baseline comparison of microcirculation and bone metabolism
Baseline comparison of microcirculation and bone metabolism among the 5 different groups

Type 2 diabetes without neuropathy

10 patients

  • Anthropometric measures: Height, weight, BMI, waist circumference
  • Vital parameters: supine and standing blood pressure, pulse, respiratory rate and temperature
  • Laboratory assessment that includes markers of endothelial activation, inflammation and bone metabolism.
  • Assessment of skin microcirculation with Laser Doppler Iontophoresis
  • Assessment of calcaneal bone mineral density (BMD) with Bone Sonometer (ultrasound)
  • Advanced glycation end-products will be assessed by an AGE reader which uses the technique of skin autofluorescence
Other: Baseline comparison of microcirculation and bone metabolism
Baseline comparison of microcirculation and bone metabolism among the 5 different groups

Type 2 diabetes with painful neuropathy

10 patients

  • Anthropometric measures: Height, weight, BMI, waist circumference
  • Vital parameters: supine and standing blood pressure, pulse, respiratory rate and temperature
  • Laboratory assessment that includes markers of endothelial activation, inflammation and bone metabolism.
  • Assessment of skin microcirculation with Laser Doppler Iontophoresis
  • Assessment of calcaneal bone mineral density (BMD) with Bone Sonometer (ultrasound)
  • Advanced glycation end-products will be assessed by an AGE reader which uses the technique of skin autofluorescence
Other: Baseline comparison of microcirculation and bone metabolism
Baseline comparison of microcirculation and bone metabolism among the 5 different groups

Type 2 diabetes with painless neuropathy

10 patients

  • Anthropometric measures: Height, weight, BMI, waist circumference
  • Vital parameters: supine and standing blood pressure, pulse, respiratory rate and temperature
  • Laboratory assessment that includes markers of endothelial activation, inflammation and bone metabolism.
  • Assessment of skin microcirculation with Laser Doppler Iontophoresis
  • Assessment of calcaneal bone mineral density (BMD) with Bone Sonometer (ultrasound)
  • Advanced glycation end-products will be assessed by an AGE reader which uses the technique of skin autofluorescence
Other: Baseline comparison of microcirculation and bone metabolism
Baseline comparison of microcirculation and bone metabolism among the 5 different groups

Type 2 diabetes with Charcot foot

10 patients

  • Anthropometric measures: Height, weight, BMI, waist circumference
  • Vital parameters: supine and standing blood pressure, pulse, respiratory rate and temperature
  • Laboratory assessment that includes markers of endothelial activation, inflammation and bone metabolism.
  • Assessment of skin microcirculation with Laser Doppler Iontophoresis
  • Assessment of calcaneal bone mineral density (BMD) with Bone Sonometer (ultrasound)
  • Advanced glycation end-products will be assessed by an AGE reader which uses the technique of skin autofluorescence
Other: Baseline comparison of microcirculation and bone metabolism
Baseline comparison of microcirculation and bone metabolism among the 5 different groups




Primary Outcome Measures :
  1. Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by: [ Time Frame: At baseline ]
    Endothelial-dependent and independent vasodilatations

  2. Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by: [ Time Frame: at baseline ]
    Markers of endothelial activation, which include adhesion molecules like ICAM, VCAM and inflammatory molecules.

  3. Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by: [ Time Frame: at baseline ]
    Serum Nitric oxide

  4. Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by: [ Time Frame: at baseline ]
    Advanced glycation end-products


Secondary Outcome Measures :
  1. Impaired bone metabolism in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as assessed by: [ Time Frame: At baseline ]
    Bone turnover markers like P1NP, CTX, Sclerostin, RANKL, OPG, OPN, OCN, BMP4 and TGF-1β.

  2. Impaired bone metabolism in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as assessed by: [ Time Frame: At baseline ]
    Calcaneal bone mineral density (BMD)


Biospecimen Retention:   Samples Without DNA
Analysis of serum samples for markers of endothelial function, inflammation and bone metabolism


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

40 patients with type 2 diabetes mellitus will be considered eligible for the study. Patients with a previous diagnosis of type 2 diabetes mellitus and newly diagnosed type 2 DM seen at Tameside Hospital will be recruited into the study. In addition, eligible patients will be identified and referred from University Hospital of South Manchester (UHSM) and appropriate GP practices (from Oldham, Tameside and Wythenshawe).

Source of healthy controls: Hospital staff and spouses/ partners of patients will volunteer as healthy subjects.

Criteria

Inclusion Criteria:

  • • Subjects aged between 40-75 years

    • Healthy subjects or non-diabetic subjects for the control group.
    • A diagnosis of type 2 DM based on one of the following criteria (ADA - 2010):
  • Fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) or
  • 2-h plasma glucose ≥ 200 mg/dl (11.1 mmol/L) during an OGTT or
  • Classic symptoms of hyperglycaemia or hyperglycaemic crisis with a random plasma glucose ≥ 200 mg/dL (11.1 mmol/L).

    • Patients on treatment for type 2 diabetes mellitus
    • Presence of diabetic neuropathy will be confirmed when 2 of the following neurological tests are positive on examination (vibration perception threshold, 10 gm. monofilament, 128 Hz tuning fork, ankle reflex, pin-prick)
    • Painful diabetic neuropathy diagnosed according to LANSS (Leeds Assessment of Neuropathic Symptoms and Signs) scoring
    • For patients with chronic Charcot foot, the diagnosis should be confirmed by clinical judgment and by radiologic examination - X-ray, technetium-labeled bisphosphonate bone scan or MRI)

Exclusion Criteria:

  • • At screening, age below 40 years and above 75 years.

    • Type 1 diabetes mellitus (patients with a history of ketoacidosis, age of onset of DM before 25 years of age, BMI <21 kg/m2 and use of insulin without a concomitant oral hypoglycemic agent)
    • Major cardiovascular complications within 3 months prior to screening
    • Recent history of smoking within the last 6 months
    • Scars, tattoos or rashes over the forearm
    • Recent or current oral steroid therapy or topical steroids applied to the forearm
    • Patients with uncontrolled hypertension (systolic blood pressure [SBP] > 160/90 mmHg) or hypotension (SBP ≤ 100 mm Hg or a diastolic BP of ≤60 mm Hg) at screening.
    • History of general systemic illness including cardiac, hepatic or renal insufficiency
    • Patients with renal insufficiency characterized by a creatinine clearance of less than 60 ml/min or a serum creatinine of more than 130 μmol/l
    • Receiving treatment for inflammatory disease or malignancy
    • Other non-diabetic causes of neuropathy
    • History of chronic alcohol consumption
    • History of metabolic bone disorders (Osteoporosis, Paget's disease, etc.) or treatment for bone disorders (past or current treatment for osteoporosis, bisphosphonate therapy within the last 3 years)
    • History of malignancy
    • History of active foot ulcers
    • History of concomitant therapy that may interfere with bone metabolism e.g. glucocorticoids (within the last 3 months), hormone replacement therapy (in the last 12 months), SERM (selective oestrogen receptor modulator), thiazolidinedione, anticonvulsant use
    • Receiving drugs that fluoresce (e.g., Doxorubicin, Daunomycin, Camptothecin, Protoporphyrin, Fluoroquinolones, Tetracycline, Hydroxychloroquine or Quinidine)
    • History of photosensitivity reactions (e.g., sensitive to ultraviolet light, or taking medication known to cause photosensitivity
    • Simultaneous participation in other clinical trials or involvement in another research trial involving an investigational product in the past 12 weeks.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02435329


Locations
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United Kingdom
Tameside Hospital NHS Foundation Trust
Ashton-under-Lyne, Greater Manchester, United Kingdom, OL6 9RW
Sponsors and Collaborators
Tameside General Hospital
Manchester Metropolitan University
Investigators
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Principal Investigator: Edward Jude, MD, MRCP Tameside Hospital NHS Foundation Trust

Publications:
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Responsible Party: Tameside General Hospital
ClinicalTrials.gov Identifier: NCT02435329     History of Changes
Other Study ID Numbers: Charcodiab13
15/NI/0043 ( Other Identifier: HSC REC A )
First Posted: May 6, 2015    Key Record Dates
Last Update Posted: September 16, 2019
Last Verified: September 2019
Additional relevant MeSH terms:
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Bone Diseases
Bone Diseases, Metabolic
Diabetic Angiopathies
Diabetes Mellitus
Diabetes Mellitus, Type 2
Metabolic Diseases
Glucose Metabolism Disorders
Endocrine System Diseases
Musculoskeletal Diseases
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications