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Trial record 66 of 87 for:    NIDDK endocrine and diabetes | Recruiting, Not yet recruiting, Available Studies

Pre-diabetes in Subject With Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)

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ClinicalTrials.gov Identifier: NCT02969798
Recruitment Status : Recruiting
First Posted : November 21, 2016
Last Update Posted : August 30, 2019
Sponsor:
Collaborators:
American Diabetes Association
AstraZeneca
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio

Brief Summary:
HYPOTHESIS: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) have distinct pathophysiologic etiologies. Therefore, therapeutic interventions designed to correct the specific underlying pathogenic abnormalities in IGT and IFG will be required to optimally prevent the progressive beta cell failure and development of overt type 2 diabetes.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Impaired Glucose Tolerance (IGT) Impaired Fasting Glucose (IFG) Drug: Dapagliflozin Drug: Saxagliptin Drug: Pioglitazone Drug: Metformin Not Applicable

Detailed Description:

SPECIFIC AIMS:

  1. To examine the effect of the following pharmacologic interventions on beta cell function, insulin sensitivity, and glucose tolerance status in individuals with isolated impaired glucose tolerance (IGT): (i) treatment with the renal Sodium-glucose co-transporter 2 (SGLT2) inhibitor inhibitor, dapagliflozin; (ii) treatment with the inhibitors of dipeptidyl peptidase 4, also DPP4, saxagliptin ; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin.
  2. To examine the effect of the following pharmacologic interventions on beta cell function, insulin sensitivity, and glucose tolerance status in individuals with isolated impaired fasting glucose (IFG): (i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin.
  3. To examine the effect of the following pharmacologic interventions on beta cell function, insulin sensitivity, and glucose tolerance status in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG): i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 700 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Preservation of Beta Cell Function in Pre-diabetes in Subject With Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)
Study Start Date : January 2014
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prediabetes

Arm Intervention/treatment
No Intervention: (i) healthy normal glucose tolerance (NGT) subjects
Subjects (Fasting Plasma Glucose or FPG < 100 mg/dl and 2-h PG < 140 mg/dl) without FH (family history) of diabetes in a first degree relative
Active Comparator: ii) healthy subjects with isolated IGT
(ii) healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive one of the following four treatments: (1) Dapagliflozin, 10 mg/day, (2) Saxagliptin, 5 mg/day (3) Pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two; (4) Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2.
Drug: Dapagliflozin
10mg/day
Other Name: farxiga

Drug: Saxagliptin
5mg/day
Other Name: onglyza

Drug: Pioglitazone
the dose will increase from 15 mg/day to 30 mg/day at month two
Other Name: actos

Drug: Metformin
starting at 1000 mg/day and increased to 2000 mg/day at month 2.
Other Name: glucophage

Active Comparator: (iii) healthy subjects with isolated IFG
(iii) healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive one of the following four treatments: (1) Dapagliflozin, 10 mg/day, (2) Saxagliptin, 5 mg/day (3) Pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two; (4) Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2.
Drug: Dapagliflozin
10mg/day
Other Name: farxiga

Drug: Saxagliptin
5mg/day
Other Name: onglyza

Drug: Pioglitazone
the dose will increase from 15 mg/day to 30 mg/day at month two
Other Name: actos

Drug: Metformin
starting at 1000 mg/day and increased to 2000 mg/day at month 2.
Other Name: glucophage

Active Comparator: (iv) healthy subjects with IGT plus IFG
(iv) healthy subjects with IGT plus IFG will receive one of the following four treatments: (1) Dapagliflozin, 10 mg/day, (2) Saxagliptin, 5 mg/day (3) Pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two; (4) Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2.
Drug: Dapagliflozin
10mg/day
Other Name: farxiga

Drug: Saxagliptin
5mg/day
Other Name: onglyza

Drug: Pioglitazone
the dose will increase from 15 mg/day to 30 mg/day at month two
Other Name: actos

Drug: Metformin
starting at 1000 mg/day and increased to 2000 mg/day at month 2.
Other Name: glucophage




Primary Outcome Measures :
  1. Beta cell function in individuals with isolated impaired glucose tolerance (IGT) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Beta cell function in individuals with isolated impaired glucose tolerance (IGT) will be measured after 24 months of: (i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin ; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Beta cell function will be measured as insulin secretion during the hyperglycemic clamp (mean plasma insulin concentration in uU/ml) multiplied by insulin sensitivity measured with the euglycemic insulin clamp (mg/kg.min).

  2. Insulin sensitivity in individuals with isolated impaired glucose tolerance (IGT) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Insulin sensitivity in individuals with isolated impaired fasting glucose (IGT) will be measured after 24 months of: (i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Insulin Sensitivity will be measured with the euqglycemic insulin clamp and expressed as mg/kg.min.

  3. Glucose tolerance status in individuals with isolated impaired glucose tolerance (IGT) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Glucose tolerance status in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG) will be measured after 24 months of:: i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Glucose tolerance status will be evaluated by measuring the HbA1c.

  4. Glucose tolerance status in individuals with isolated impaired glucose tolerance (IGT) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Glucose tolerance status in individuals with impaired glucose tolerance (IGT) will be measured after 24 months of:: i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin.Glucose tolerance status will be evaluated by measuring fasting plasma glucose concentration (mg/dl).

  5. Glucose tolerance status in individuals with isolated impaired glucose tolerance (IGT) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Glucose tolerance status in individuals with impaired glucose tolerance (IGT) will be measured after 24 months of:: i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Glucose tolerance status will be evaluated by 2-hour plasma glucose concentration (mg/dl) during the OGTT.

  6. Beta cell function in individuals with isolated impaired fasting glucose (IFG) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Beta cell function in individuals with isolated impaired fasting glucose (IFG) will be measured after 24 months of: (i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Beta cell function will be measured as insulin secretion during the hyperglycemic clamp (mean plasma insulin concentration in uU/ml) multiplied by insulin sensitivity measured with the euglycemic insulin clamp (mg/kg.min).

  7. Insulin sensitivity in individuals with isolated impaired fasting glucose (IFG) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Insulin sensitivity in individuals with isolated impaired fasting glucose (IFG) will be measured after 24 months of: (i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Insulin Sensitivity will be measured with the euqglycemic insulin clamp and expressed as mg/kg.min.

  8. Glucose tolerance status in individuals with isolated impaired fasting glucose (IFG) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Glucose tolerance status in individuals with isolated impaired fasting glucose (IFG) will be quantitated after 24 months of: (i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Glucose tolerance status will be evaluated by measuring the fasting plasma glucose concentration (mg/dl).

  9. Glucose tolerance status in individuals with isolated impaired fasting glucose (IFG) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Glucose tolerance status in individuals with isolated impaired fasting glucose (IFG) will be quantitated after 24 months of: (i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Glucose tolerance status will be evaluated by measuring the HbA1c (%).

  10. Glucose tolerance status in individuals with isolated impaired fasting glucose (IFG) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Glucose tolerance status in individuals with isolated impaired fasting glucose (IFG) will be quantitated after 24 months of: (i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Glucose tolerance status will be evaluated by measuring the and 2-hour plasma glucose concentration (mg/dl) during the OGTT.

  11. Beta cell function in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Beta cell function in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG) will be measured after 24 months of:: i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Beta cell function will be measured as insulin secretion during the hyperglycemic clamp (mean plasma insulin concentration in uU/ml) multiplied by insulin sensitivity measured with the euglycemic insulin clamp (mg/kg.min).

  12. Insulin sensitivity in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Insulin sensitivity in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG) will be measured after 24 months of:: i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Insulin Sensitivity will be measured with the euqglycemic insulin clamp and expressed as mg/kg.min.

  13. Glucose tolerance status in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Glucose tolerance status in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG) will be measured after 24 months of:: i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Glucose tolerance status will be evaluated by measuring the HbA1c (%).

  14. Glucose tolerance status in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Glucose tolerance status in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG) will be measured after 24 months of:: i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Glucose tolerance status will be evaluated by measuring the fasting plasma glucose concentration (mg/dl).

  15. Glucose tolerance status in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG) will be measured. [ Time Frame: 24 months after treatment phase begins ]
    Glucose tolerance status in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG) will be measured after 24 months of:: i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. Glucose tolerance status will be evaluated by measuring the 2-hour plasma glucose concentration (mg/dl) during the OGTT.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • NGT subjects will serve as controls and will be matched in age, gender, ethnicity, and BMI to IGT and IFG subjects

    1. Male or female subjects between the ages of 18 and 65 years of age, inclusive, at Screening.
    2. FPG < 100 mg/dl and 2-h PG < 140 mg/dl
    3. BMI = 24-40 kg/m2;
    4. Stable body weight (±4lbs) over the preceding 3 months
    5. Subjects with no evidence of major organ system disease as determined by physical exam, history, and screening laboratory data
    6. Females of childbearing potential with a negative pregnancy test at Screening and Treatment visits, using one of the following forms of contraception for the duration of participation in the study (i.e., until Follow-up 7-14 days post last dose):

      • Oral contraceptive
      • Injectable progesterone
      • Subdermal implant
      • Spermicidal foam/gel/film/cream/suppository
      • Diaphragm with spermicide
      • Copper or hormonal containing IUD
      • Sterile male partner vasectomized > 6 month pre-dosing.
    7. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
    8. Subjects must be willing and able to comply with scheduled visits, treatment, laboratory tests and study procedures.

Exclusion Criteria:

  1. Recent (i.e., within three (3) months prior to Screening) evidence or medical history of unstable concurrent disease such as: documented evidence or history of clinically significant hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, immunological, or clinically significant neurological disease.
  2. Subjects with a family history of diabetes in a first degree relative
  3. BMI of less than 24 or greater than 40 kg/m2
  4. Unstable body weight (change of greater than ±4lbs over the preceding 3 months
  5. Subjects participating in an excessively heavy exercise program
  6. Subject with a feeding/sleeping schedule different from a daytime feeding/night time sleeping schedule
  7. Subjects taking medications known to alter glucose metabolism (with the exception of metformin and/or pioglitazone) or which effect brain neurosynaptic function are excluded.
  8. Subjects with evidence of major organ system disease as determined by physical exam, history, and screening laboratory data
  9. Pregnant subjects or subjects unwilling to use birth control during their study enrollment
  10. Blood donation of approximately 1 pint (500 mL) within 8 weeks prior to Screening.
  11. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
  12. Subjects with hematuria will be excluded.
  13. Subjects with evidence or prior history of heart failure will be excluded
  14. Subjects with family history of pancreatic, bladder, and breast cancer will be excluded.
  15. Subjects with history of pancreatitis will be excluded.
  16. Subjects with eGFR < 60 ±5 ml/min.1.73m2 will be excluded.
  17. Subjects with elevated serum creatinine (>1.5 mg/dl males/1.4 mg/dl females) will be excluded.
  18. Subjects with a history of orthostatic hypotension (>15/10 mmHg) will be excluded.
  19. Subjects with liver enzymes (ALT, AST) >3-fold above upper normal limit will be excluded.
  20. Subjects with a history of hypersensitivity to pioglitazone, dapagliflozin, or Saxagliptin will be excluded.

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): NCT02969798


Contacts
Layout table for location contacts
Contact: Ralph A DeFronzo, MD 210-567-6691 defronzo@uthscsa.edu
Contact: Monica Palomo, BS 210-567-6710 palomom@uthscsa.edu

Locations
Layout table for location information
United States, Texas
The University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Ralph A DeFronzo, MD    210-567-6691    defronzo@uthscsa.edu   
Contact: Monica Palomo, BS    210-567-6710    palomom@uthscsa.edu   
Principal Investigator: Ralph A DeFronzo, MD         
Sub-Investigator: Eugenio Cersosimo, MD         
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
American Diabetes Association
AstraZeneca
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Layout table for investigator information
Principal Investigator: Ralph A DeFronzo, MD The University of Texas Health Science Center at San Antonio

Layout table for additonal information
Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT02969798     History of Changes
Other Study ID Numbers: HSC20130414H
R01DK024092-34 ( U.S. NIH Grant/Contract )
First Posted: November 21, 2016    Key Record Dates
Last Update Posted: August 30, 2019
Last Verified: August 2019
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Intolerance
Prediabetic State
Glucose Metabolism Disorders
Metabolic Diseases
Hyperglycemia
Metformin
Pioglitazone
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Saxagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors