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Trial record 3 of 9 for:    XBP1

Role of Endoplasmic Reticulum Stress in the Pathophysiology of Type 2 Diabetes (GLUCOSTRESS)

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: NCT02368704
Recruitment Status : Unknown
Verified April 2016 by Assistance Publique - Hôpitaux de Paris.
Recruitment status was:  Active, not recruiting
First Posted : February 23, 2015
Last Update Posted : April 18, 2016
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

The purpose of this study is to investigate whether Endoplasmic Reticulum (ER) stress pathway is activated in peripheral tissues (adipose tissue) in insulin resistant diabetic patients compared to healthy subjects normoglycemic matched for age and sex an to investigate whether ER stress pathway can be activated in response to insulin. Indeed, some preliminar on rates studies shows that ER stress pathway is activated by insulin in liver and adipose tissue showing that hyperinsulinemia might help trigger stress path ER.

For this, we propose a case control study of type 2 diabetic patients vs control subjects in which markers of ER stress will be evaluated from abdominal subcutaneous adipose tissue obtained before and after euglycemic hyperinsulinemic. We chose to consider adipose tissue subcutaneous rather than visceral adipose tissue for obvious reasons of lesser invasiveness.


Condition or disease Intervention/treatment
Diabetes Mellitus, Type 2 Endoplasmic Reticulum Stress Other: No intervention

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Study Type : Observational
Actual Enrollment : 40 participants
Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Role of Endoplasmic Reticulum Stress in the Pathophysiology of Type 2 Diabetes
Study Start Date : November 2012
Estimated Primary Completion Date : November 2016
Estimated Study Completion Date : November 2016

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
control

control subjects with :

  • Nondiabetic subjects (blood glucose <7.0 mmol/l without hypoglycemic treatment).
  • The control subjects should be matched to patients for age (± 5 years), sex, and BMI (± 2 kg/m2).
Other: No intervention
case

Diabetic patients with :

  • Having type 2 diabetes for at least 6 months
  • HbA1c ≤ 8%
  • Treat by lifestyle and dietary rules associated or not to a hypoglycemic therapy (metformin and / or sulfamid) and / or insulin secretors dependent glucose as inhibitors of DPP4 (dipeptidyl peptidase-4): Vildagliptin, Sitagliptin, Saxagliptin
  • No modification of hypoglycemic therapy and / or insulin secretors for at least 3 months
Other: No intervention



Primary Outcome Measures :
  1. Show an increase in markers of ER stress in fasting patients with type 2 diabetes [ Time Frame: 2 days ]
    Protein expression markers of ER stress pathway BiP / GRP 78, CHOP, ATF4 EDEM and XBP-1


Secondary Outcome Measures :
  1. Assess whether insulin induces an increase in markers of ER stress [ Time Frame: 2 days ]
    Insulin sensitivity

  2. Insulin secretion in response to glucose infusion [ Time Frame: 2 days ]
  3. Insulin secretion in response to arginine infusion [ Time Frame: 2 days ]
  4. Lipolysis on insulin [ Time Frame: 2 days ]

Biospecimen Retention:   Samples With DNA
blood samples. These samples will be anonymized, frozen and stored in the INSERM UMR-S 872 in the Cordeliers Research Center (Madame Fabienne Foufelle) under the responsibility of Professor Jean-François Gautier for a maximum period of 15 years, beyond which they will be destroyed. These samples will be destroyed at any time at the request of the patient. This DNA storage will be used to study genes related to the secretion of insulin and to identify other genes involved in the onset of diabetes.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients with type 2 diabetes Healthy volunteers Adults
Criteria

Inclusion Criteria:

  • Specific criteria for diabetic patients:
  • Having type 2 diabetes for at least 6 months
  • HbA1c ≤ 8%
  • Treated by lifestyle and dietary rules associated or not to a hypoglycemic therapy (metformin and / or sulfamid) and / or insulin secretors dependent glucose as inhibitors of DPP4 (dipeptidyl peptidase-4): Vildagliptin, Sitagliptin, Saxagliptin
  • No modification of hypoglycemic therapy and / or insulin secretors for at least 3 months

Specific criteria for control subjects:

  • Nondiabetic subjects (fasting blood glucose <7.0 mmol / l without hypoglycemic treatment).
  • The control subjects should be matched to patients for age (± 5 years), sex, and BMI (± 2 kg/m2).

Common criteria for patients and control subjects:

  • Aged 18 to 60 years
  • Body Mass Index between 25 and 35 kg/m2
  • Accepting the constraints of the protocol and who signed the informed consent
  • Systolic blood pressure < 160 mmHg, diastolic blood pressure < 90 mm Hg (with or without antihypertensive treatment)
  • Resting heart rate between 55 and 100 beats/min.
  • Normal laboratory tests or not clinically significant abnormality for NFS platelets, PT, aPTT, fibrinogen ALT, AST, GGT, Serum electrolytes, urea, creatinine, Uric acid Triglycerides, total cholesterol, HDL cholesterol
  • HCG negative blood (for female subjects)
  • Affiliated to the Social Security.

Exclusion Criteria:

  • Current infections or recent infections (<10 days)
  • Neoplastic disorders (with the exception of carcinoma in situ of the cervix or cutaneous epithelioma), haematological, cardiovascular, psychiatric, neurological
  • Poisoning smoking (>10 cigarettes per day, what ever the duration of intoxication)
  • Treatment with insulin or glitazones Pregnancy, Breastfeeding
  • Body Mass Index > 35 kg/m2
  • Any drug taken for less than 8 days without the inclusion of minor analgesics (aspirin, paracetamol), anti-hypertensive medications, oral hypoglycemic (metformin and sulphonylureas) and insulin secretors dependent glucose as inhibitors of DPP4 (dipeptidyl peptidase-4) and oral contraceptives.

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): NCT02368704


Locations
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France
Saint-Louis Hospital
Paris, France, 75010
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02368704     History of Changes
Other Study ID Numbers: GLUCOSTRESS P 08 11 22
First Posted: February 23, 2015    Key Record Dates
Last Update Posted: April 18, 2016
Last Verified: April 2016

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Endoplasmic Reticulum

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases