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Trial record 21 of 27 for:    "Marfan syndrome"

Glucose-dependent Asprosin Dynamics

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ClinicalTrials.gov Identifier: NCT03358121
Recruitment Status : Completed
First Posted : November 30, 2017
Last Update Posted : November 30, 2017
Sponsor:
Information provided by (Responsible Party):
Stefan Kopf MD, Heidelberg University

Brief Summary:
The study entitled " Asprosin Dynamics relating to serum Glucose levels under controlled alterations" investigates the dynamics of Asprosin in relation to glucose levels under controlled conditions in diabetic patients.

Condition or disease Intervention/treatment
Diabetes Mellitus Diagnostic Test: Clamp study

Detailed Description:

The Pilot study entitled Asprosin Dynamics relating to serum Glucose levels under controlled alterations is designed to date the asprosin kinetics at various metabolic states relating to serum glucose and the correlation between asprosin and the known glucose regulating hormones. Asprosin is the C-terminal cleavage product of profibrilln. This new hormone is encoded by FBN1 Gen (Amino acid residues 2732 to 2871, molecular weight 30 kDa), which also encodes fibrillin. The hormone was initially discovered during the analysis of the genome of patients with the extremely rare Wiedemann Rautenstrauch syndrome. According to the data so far, asprosin is a fast induced protein hormone that acts on the liver through cell membrane receptors, where it activates the G protein cAMP PKA pathway, leading to a rapid release of glucose into the circulation and to compensatory insulin production. The above seems to match the constellation found in overweight type 2 diabetes patients or patients with metabolic syndrome (insulin resistance). Diabetic mice were able to normalize their glucose and insulin levels by asprosin-binding antibodies. According to a recent study, asprosin had no influence on the serum concentration of glucagon, epinephrine, norepinephrine and cortisol in mice. In humans it is known that asprosin increases during fasting.

The liver related glucose release into the blood circulation is crucial for the brain function and overall survival during fasting. In addition, a compensatory rise in asprosin is expected during a hypoglycemic episode. In this pilot study, the asprosin concentration is measured both in participants with type 1 Diabetes mellitus, with or without hypoglycemia unawareness during a hypoglycemic phase. These relevant measurements are compared in the two subgroups, consisting of 5 persons each. By correlating asprosin values with other regulating hormones, there is hope to better understand the pathomechanism of hypoglycemia unawareness. Recently discovered is that the recombinant asprosin administration in mice allows both the blood glucose and the insulin to rise. It is therefore very likely that further studying of asprosin could provide new insights into the (patho) physiology of the intermediary metabolism disorder.

According to the above, the following hypotheses arise:

Asprosin dynamics relating to serum Glucose levels under controlled alteration:

Asprosin, as fast induced protein hormone, increases serum levels in type 1 diabetics with or without diabetes late complications during a hypoglycemic phase. Asprosin increases serum levels more significantly in diabetics without hypoglycemia unawareness compared to diabetics with hypoglycemia unawareness. There is probably no correlation between asprosin and the previous known regulating hormones. In order to investigate these hypotheses, study participants will be initially profoundly examined in our Clinical Study Center regarding both their glycemic metabolical responses and the clinical findings relating to their possible micro- and macrovascular complications. In addition to this quality of life, well being, depression and neuropathic pain is going to be taken into account. This is to be the first study of its kind, in which plasma levels of asprosin is determined and Type 1 diabetics with and without hypoglycemia unawareness are thoroughly examined in order to identify possible differences and similarities for the better determination of the new hormone utilizing the framework of hyperinsulinemic Clamp Tests. The intention behind is to better understand the (patho) physiology of the hypoglycaemia unawareness, as well as to better characterize the physiological properties of asprosin


Study Type : Observational
Actual Enrollment : 10 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Asprosin Dynamics Relating to Serum Glucose Levels Under Controlled Alteration
Actual Study Start Date : July 11, 2017
Actual Primary Completion Date : October 13, 2017
Actual Study Completion Date : October 13, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Marfan Syndrome

Group/Cohort Intervention/treatment
Diabetics without hypoglycemia awareness
Diabetic patients without impaired hypoglycemia awareness. No interventions were performed, the study is purely observational.
Diagnostic Test: Clamp study
Clamp study to achieve high, normal, and lower glucose levels to study the dynamics of Asprosin.

Diabetics with hypoglycemia awareness
Diabetic patients with impaired hypoglycemia awareness. No interventions were performed, the study is purely observational.
Diagnostic Test: Clamp study
Clamp study to achieve high, normal, and lower glucose levels to study the dynamics of Asprosin.




Primary Outcome Measures :
  1. Asprosin dynamics [ Time Frame: during clamp study, five hours ]

    Euglycemic hyperinsulinemic clamp It is a scientific test for the determination tissue sensitivity to insulin. The asprosin kinetic in various hyperglycemic and euglycemic phases as well as the correlation between asprosin levels to the other known regulating hormones will be investigated.

    An intravenous glucose tolerance test takes place in the morning and the serum glucose is controlled. Afterwards glucose 20 percent and insulin solution normal insulin is infused in order to set serum glucose manually at a target value of 90 mg per dl. The same test is performed with a glucose serum level of about 60 mg per dl, corresponding to physiological fasting serum glucose values. This is done in order to be able to assess asprosin kinetics even at lower serum glucose levels. At the end of this last hour, blood tests for the hormone measurement are performed. The duration of the examination is approximately 5 hours. Measurement of Asprosin is analyzed by ELISA



Biospecimen Retention:   Samples With DNA
Biobank, including serum and EDTA plasma.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
10 diabetic patients, five with and five without impairment in hypoglycemia awareness were included in the study.
Criteria

Inclusion criteria for participants without hypoglycemia unawareness

  • Age between 18 and 75 years
  • BMI between 20 und 35 kg per m2
  • Persons with manifest diabetes mellitus type 1 and diagnosis according to according to DDG guidelines 2011 oGTT, HbA1c more than 6.5 percent in the absence of adulteration of the HbA1c, over 200 mg per dl in the 2 hour value of the oGTT, fasting glucose more than 126 mg per dl, spontaneous glucose more than 200 mg per dl at least twice.

Inclusion criteria for participants without hypoglycemia unawareness

  • Persons who are not aware of hypoglycemia symptoms at glucose levels above 50 mg per dl
  • Age between 18 and 75 years
  • BMI between 20 und 35 kg per m2
  • Persons with manifest diabetes mellitus type 1 and diagnosis according to DDG guidelines 2011 oGTT, HbA1c more than 6.5 percent in the absence of adulteration of the HbA1c, over 200 mg per dl in the 2 hour value of the oGTT, fasting glucose more than 126 mg per dl, spontaneous glucose more than 200 mg per dl at least twice.

General exclusion criteria Secondary types of diabetes (ADA criteria type 3 B to H)

  • Current pregnancy
  • Acute infections or fever Immune-suppressant therapy
  • Severe psychiatric diseases requiring treatment (for example personality disorders, schizophrenia, depression)
  • Known alcohol or drug dependency
  • Severe heart, kidney, or liver insufficiency NYHA stadium IV
  • Non-diabetic liver disease (for example PBC, PSC, Wilson's disease, hemochromatosis, autoimmune hepatitis)
  • severe peripheral artery disease (stadium IV)
  • non-diabetic glomerulopathy
  • Cancer or other malignant diseases within the last 5 years
  • Infectious diseases like hepatitis B, C, E, or HIV
  • Other severe autoimmune diseases
  • Current participation in an interventional study
  • Anemia or disorders of bone marrow Exclusion criteria for clamp study
  • Past history of deep vein thrombosis or pulmonary embolism
  • Routine laboratory test results less than 80 percent below lower reference value: Ferritin, iron, leucocytes, haemoglobin, hematocrit, RBC, platelets, blood alcohol levels.

Exclusion criteria for bioimpedance

  • measurement Pacemaker or ICD
  • Exclusion criteria for lung function testing Ignoring or non-understanding of the instructions

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): NCT03358121


Locations
Germany
Medizinische Klinik, University Hospital
Heidelberg, Baden-Wuerttemberg, Germany, 60120
Sponsors and Collaborators
Heidelberg University
Investigators
Principal Investigator: Stef Kopf, MD Head of the Clinical Study Center for Diabetes Research
  Study Documents (Full-Text)

Documents provided by Stefan Kopf MD, Heidelberg University:
Study Protocol  [PDF] May 31, 2017
Statistical Analysis Plan  [PDF] May 31, 2017


Additional Information:
Responsible Party: Stefan Kopf MD, Head of the Clinical Study Center for Diabetes Research, Heidelberg University
ClinicalTrials.gov Identifier: NCT03358121     History of Changes
Other Study ID Numbers: S-550/2016
First Posted: November 30, 2017    Key Record Dates
Last Update Posted: November 30, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

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