Diabetic AngiopathiesNCT02435329
Microcirculation and Bone Metabolism in Patients With Type 2 Diabetes Mellitus and Charcot Foot - A Pilot Study
An observational study of Diabetic Angiopathies and Bone Diseases, Metabolic, run by Tameside General Hospital at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetic Angiopathies, Bone Diseases, Metabolic
- What is being tested?
- Baseline comparison of microcirculation and bone metabolism
- How many people
- 31 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2015to Nov 2016
- 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 40 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- • 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).
Show all 10Show fewer
- 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)
Who cannot join
- • 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
Show all 19Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Tameside Hospital NHS Foundation Trust
Ashton-under-Lyne, Greater Manchester, OL6 9RW
About this study
Official title: Bone Metabolism and Endothelial Function in Patients With Type 2 Diabetes Mellitus and Charcot Foot - an Observational Comparative Study
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).
Read more
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.
Read the detailed description
This is an observational study aimed at observing and comparing differences in bone metabolism and microcirculation in patients with type 2 diabetes and healthy controls.
In this study, 50 participants will be recruited and then categorised into the following groups:
- Control group: 10 healthy volunteers (Hospital staff and spouses/ partners of patients will volunteer as healthy subjects)
- Type 2 diabetic patients without neuropathy: 10
- Type 2 diabetic patients with neuropathy:
- 10 patients with painless neuropathy
- 10 patients with painful neuropathy
- Type 2 diabetic patients with unilateral Charcot foot: 10
Visit Schedule The estimated time for enrollment of patients will be within 3 months. The duration of the study is 5 months.
Screening (-2 Weeks): To assess for eligibility. This will include informed consent process, medical history and physical examination, screening for neuropathy and routine bloods. Laboratory work-up done at screening will be considered for data analysis.
Visit 1 - Baseline visit
- 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.
- Markers of endothelial activation will be investigated using systemic protein suspension array technology. For e.g. adhesion molecules like ICAM, VCAM and inflammatory molecules.
- Nitric oxide will be analysed using Griess assay
- Bone turnover markers [e.g., P1NP (Procollagen type 1 amino terminal propeptide), CTX (C-terminal cross-linked telopeptide of type-I collagen), Sclerostin, RANKL (receptor activator for nuclear factor (NF)-kB (RANK) ligand), OPG (osteoprotegerin), OPN (osteopontin), OCN (osteocalcin), BMP4 (Bone morphogenetic protein 4) and TGF-1β(Transforming growth factor-1β) - using ELISA (enzyme-linked immunosorbent assay).
- IL-6 - Interleukin-6, an inflammatory cytokine implicated in osteoporosis (using ELISA)
- 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
Clinical Procedures
Assessment of the microcirculation with Laser Doppler Iontophoresis:
A standard measurement of microcirculation is laser Doppler iontophoresis, which is used by several research institutes. In this trial the skin microcirculation will be measured on the dorsum of the foot using a Perimed Laser Doppler imager and iontophoresis system.
Endothelial-mediated vasodilation will be measured by the iontophoresis of acetylcholine, while sodium nitroprusside will be used to measure endothelium-independent vasodilation. The iontophoresis system consists of an ION chamber (iontophoresis delivery vehicle device) that sticks firmly to the skin and a reference electrode. The response in blood flow will be imaged and quantified using the Perimed Laser Doppler Imager (PeriScan PIMII; Perimed, Sweden).
Analysis of AGE:
An AGE reader, which utilizes the principle of skin autofluorescence, will measure the accumulation of AGE in the skin. This validated device provides a real-time, non-invasive assessment of cardiovascular risk for chronic diseases like Diabetes, renal failure, cardiovascular disease, etc. AGE-modified proteins have autofluorescent properties and when excited by ultraviolet (UV) light they emit fluorescence in particular wavelengths. The levels of AGE in skin correlate with AGE levels in blood.
The volar aspect of the forearm will be placed on the AGE reader, which is equipped with a UV light source. The UV light triggers AGE in skin, after penetrating 1mm of the dermis, to emit autofluorescence that is then detected by the AGE reader. The intensity of fluorescence correlates with the quantity of AGE in the skin.
Assessment of calcaneal BMD:
This is a simple and convenient method to assess peripheral BMD and assess fracture risk. The device used is a quantitative ultrasound called Sahara Clinical Bone Sonometer (Sahara Clinical Bone Sonometer; Hologic, Waltham, MA). The calcaneus is the preferred peripheral site to assess fracture risk. This device uses ultrasound waves to determine the BMD of the calcaneus. In this procedure, once the bare heel is placed in the device, the BMD is calculated within 30 seconds and the results are then generated on paper by the device.
- Conditions
- Diabetic Angiopathies, Bone Diseases, Metabolic
- Being tested
- Baseline comparison of microcirculation and bone metabolism
- Medical subject headings
- Diabetic Angiopathies, Bone Diseases, Metabolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Baseline comparison of microcirculation and bone metabolismOther
Baseline comparison of microcirculation and bone metabolism among the 5 different groups
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: Baseline comparison of microcirculation and bone metabolism | |
| 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 Receives: Other: Baseline comparison of microcirculation and bone metabolism | |
| 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 Receives: Other: Baseline comparison of microcirculation and bone metabolism | |
| 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 Receives: Other: Baseline comparison of microcirculation and bone metabolism | |
| 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 Receives: Other: Baseline comparison of microcirculation and bone metabolism |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by:
Endothelial-dependent and independent vasodilatations
Measured: At baseline
Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by:
Markers of endothelial activation, which include adhesion molecules like ICAM, VCAM and inflammatory molecules.
Measured: at baseline
Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by:
Serum Nitric oxide
Measured: at baseline
Impaired endothelial function in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as measured by:
Advanced glycation end-products
Measured: at baseline
Secondary outcomes (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:
Bone turnover markers like P1NP, CTX, Sclerostin, RANKL, OPG, OPN, OCN, BMP4 and TGF-1β.
Measured: At baseline
Impaired bone metabolism in patients with type 2 DM with/ without diabetic neuropathy and Charcot foot compared to their healthy counterparts as assessed by:
Calcaneal bone mineral density (BMD)
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2015 (estimated)
- Study startJun 2015
- Primary completionNov 2016
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Diabetic AngiopathiesStudies of the same condition, open and under way.
- 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
- Other
- Time perspective
- Prospective
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tameside General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Manchester Metropolitan University
- Responsible party
- Sponsor
- Investigators
- Edward Jude, MD, MRCP, Principal investigator, Tameside Hospital NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02435329
- Sponsor's protocol ID
- Charcodiab13
- Other IDs
- 15/NI/0043
- Status last verified
- Sep 2019
- First submitted
- 27 Apr 2015
- Last updated
- 16 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Mascarenhas JV, Jude EB. Pathogenesis and medical management of diabetic Charcot neuroarthropathy. Med Clin North Am. 2013 Sep;97(5):857-72. doi: 10.1016/j.mcna.2013.05.002.
PubMed 23992897Hofbauer LC, Brueck CC, Singh SK, Dobnig H. Osteoporosis in patients with diabetes mellitus. J Bone Miner Res. 2007 Sep;22(9):1317-28. doi: 10.1359/jbmr.070510.
PubMed 17501667Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis. Osteoporos Int. 2007 Apr;18(4):427-44. doi: 10.1007/s00198-006-0253-4. Epub 2006 Oct 27.
PubMed 17068657Wimalawansa SJ. Nitric oxide: new evidence for novel therapeutic indications. Expert Opin Pharmacother. 2008 Aug;9(11):1935-54. doi: 10.1517/14656566.9.11.1935.
PubMed 18627331Roberts AC, Porter KE. Cellular and molecular mechanisms of endothelial dysfunction in diabetes. Diab Vasc Dis Res. 2013 Nov;10(6):472-82. doi: 10.1177/1479164113500680. Epub 2013 Sep 3.
PubMed 24002671Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007 Jan;87(1):315-424. doi: 10.1152/physrev.00029.2006.
PubMed 17237348
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bone Metabolism and Endothelial Function in Patients With Type 2 Diabetes Mellitus and Charcot Foot - an Observational Comparative Study
- ClinicalTrials.gov ID
- NCT02435329
- Acronym / sponsor ID
- Charcodiab13
- Conditions
- Diabetic Angiopathies, Bone Diseases, Metabolic
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Tameside General HospitalUniversity, hospital or other
- Collaborators
- Manchester Metropolitan University
- Study start
- Jun 2015 (actual)
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 6 May 2015 (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.
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.
Detailed description
This is an observational study aimed at observing and comparing differences in bone metabolism and microcirculation in patients with type 2 diabetes and healthy controls.
In this study, 50 participants will be recruited and then categorised into the following groups:
- Control group: 10 healthy volunteers (Hospital staff and spouses/ partners of patients will volunteer as healthy subjects)
- Type 2 diabetic patients without neuropathy: 10
- Type 2 diabetic patients with neuropathy:
- 10 patients with painless neuropathy
- 10 patients with painful neuropathy
- Type 2 diabetic patients with unilateral Charcot foot: 10
Visit Schedule The estimated time for enrollment of patients will be within 3 months. The duration of the study is 5 months.
Screening (-2 Weeks): To assess for eligibility. This will include informed consent process, medical history and physical examination, screening for neuropathy and routine bloods. Laboratory work-up done at screening will be considered for data analysis.
Visit 1 - Baseline visit
- 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.
- Markers of endothelial activation will be investigated using systemic protein suspension array technology. For e.g. adhesion molecules like ICAM, VCAM and inflammatory molecules.
- Nitric oxide will be analysed using Griess assay
- Bone turnover markers [e.g., P1NP (Procollagen type 1 amino terminal propeptide), CTX (C-terminal cross-linked telopeptide of type-I collagen), Sclerostin, RANKL (receptor activator for nuclear factor (NF)-kB (RANK) ligand), OPG (osteoprotegerin), OPN (osteopontin), OCN (osteocalcin), BMP4 (Bone morphogenetic protein 4) and TGF-1β(Transforming growth factor-1β) - using ELISA (enzyme-linked immunosorbent assay).
- IL-6 - Interleukin-6, an inflammatory cytokine implicated in osteoporosis (using ELISA)
- 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
Clinical Procedures
Assessment of the microcirculation with Laser Doppler Iontophoresis:
A standard measurement of microcirculation is laser Doppler iontophoresis, which is used by several research institutes. In this trial the skin microcirculation will be measured on the dorsum of the foot using a Perimed Laser Doppler imager and iontophoresis system.
Endothelial-mediated vasodilation will be measured by the iontophoresis of acetylcholine, while sodium nitroprusside will be used to measure endothelium-independent vasodilation. The iontophoresis system consists of an ION chamber (iontophoresis delivery vehicle device) that sticks firmly to the skin and a reference electrode. The response in blood flow will be imaged and quantified using the Perimed Laser Doppler Imager (PeriScan PIMII; Perimed, Sweden).
Analysis of AGE:
An AGE reader, which utilizes the principle of skin autofluorescence, will measure the accumulation of AGE in the skin. This validated device provides a real-time, non-invasive assessment of cardiovascular risk for chronic diseases like Diabetes, renal failure, cardiovascular disease, etc. AGE-modified proteins have autofluorescent properties and when excited by ultraviolet (UV) light they emit fluorescence in particular wavelengths. The levels of AGE in skin correlate with AGE levels in blood.
The volar aspect of the forearm will be placed on the AGE reader, which is equipped with a UV light source. The UV light triggers AGE in skin, after penetrating 1mm of the dermis, to emit autofluorescence that is then detected by the AGE reader. The intensity of fluorescence correlates with the quantity of AGE in the skin.
Assessment of calcaneal BMD:
This is a simple and convenient method to assess peripheral BMD and assess fracture risk. The device used is a quantitative ultrasound called Sahara Clinical Bone Sonometer (Sahara Clinical Bone Sonometer; Hologic, Waltham, MA). The calcaneus is the preferred peripheral site to assess fracture risk. This device uses ultrasound waves to determine the BMD of the calcaneus. In this procedure, once the bare heel is placed in the device, the BMD is calculated within 30 seconds and the results are then generated on paper by the device.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers | – | Other: Baseline comparison of microcirculation and bone metabolism10 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 |
| Type 2 diabetes without neuropathy | – | Other: Baseline comparison of microcirculation and bone metabolism10 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 |
| Type 2 diabetes with painful neuropathy | – | Other: Baseline comparison of microcirculation and bone metabolism10 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 |
| Type 2 diabetes with painless neuropathy | – | Other: Baseline comparison of microcirculation and bone metabolism10 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 |
| Type 2 diabetes with Charcot foot | – | Other: Baseline comparison of microcirculation and bone metabolism10 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 |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (10 listed)
- • Subjects aged between 40-75 years
- 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).
Key exclusion criteria (19 listed)
- • At screening, age below 40 years and above 75 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Baseline comparison of microcirculation and bone metabolismBaseline comparison of microcirculation and bone metabolism among the 5 different groups | Other | Healthy volunteers, Type 2 diabetes with Charcot foot, Type 2 diabetes with painful neuropathy, Type 2 diabetes with painless neuropathy, Type 2 diabetes without neuropathy |
Primary outcome
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
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.
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
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
2 secondary outcomes
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
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
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 16 Sep 2019.
- Background: PubMed 23992897Mascarenhas JV, Jude EB. Pathogenesis and medical management of diabetic Charcot neuroarthropathy. Med Clin North Am. 2013 Sep;97(5):857-72. doi: 10.1016/j.mcna.2013.05.002.
- Background: PubMed 17501667Hofbauer LC, Brueck CC, Singh SK, Dobnig H. Osteoporosis in patients with diabetes mellitus. J Bone Miner Res. 2007 Sep;22(9):1317-28. doi: 10.1359/jbmr.070510.
- Background: PubMed 17068657Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis. Osteoporos Int. 2007 Apr;18(4):427-44. doi: 10.1007/s00198-006-0253-4. Epub 2006 Oct 27.
- Background: PubMed 18627331Wimalawansa SJ. Nitric oxide: new evidence for novel therapeutic indications. Expert Opin Pharmacother. 2008 Aug;9(11):1935-54. doi: 10.1517/14656566.9.11.1935.
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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.
Edward Jude, MD, MRCP principal investigator
Tameside Hospital NHS Foundation Trust
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 Diabetic Angiopathies and Bone Diseases, Metabolic, run by Tameside General Hospital at 1 site in United Kingdom.
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 10 inclusion and 19 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 16 Sep 2019. 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 United Kingdom. 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?
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). 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 NCT02435329, which also lists 6 linked publications.
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 16 Sep 2019.