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HbA1c Variability in Type II Diabetes

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ClinicalTrials.gov Identifier: NCT02879409
Recruitment Status : Unknown
Verified June 2017 by Weill Cornell Medical College in Qatar.
Recruitment status was:  Recruiting
First Posted : August 25, 2016
Last Update Posted : June 2, 2017
Sponsor:
Collaborators:
Hamad Medical Corporation
Sidra Medical and Research Center
University of Hull
Information provided by (Responsible Party):
Weill Cornell Medical College in Qatar

Brief Summary:

There are numerous possible reasons why it could be speculated that HbA1c variability may affect complication risk. Of interest are the concepts that both laboratory and clinic evidence suggests that periods of sustained hyperglycemia are 'remembered' (metabolic memory), this in turn is recognized to place patients at greater long-term risk of complications. As such it can be speculated that the detrimental effect of variability in HbA1c may be mediated via the same mechanism as 'metabolic memory' phenomenon.

Aims: To determine whether treatment to one of 2 threshold levels will result in one group of type 2 diabetes patients having the same mean HbA1c but with differing HbA1c variability to that of another and related to markers of oxidative stress, inflammation and microvascular complications. To determine whether a difference in HbA1c variability between the 2 groups will reflect in changes in small nerve fibers assessed with the sensitive method of corneal confocal microscopy and cardiac autonomic function testing. To assess the reproducibility of HbA1c measurement from a whole blood samples initially analyzed and then stored at -80C until the end of the study (2-3 years), as well as storing an aliquot of haemolysate, for reanalysis at the end of the study.

In one arm the investigators will intensify treatment in those with FPG>140mg/dl until their FPG is <90mg/dl, using whatever treatment is clinically appropriate for them, and only intensify it further if their FPG rises to >140mg/dl again. In the other group the investigators will intensify if their FPG is >115 mg/dl until it is <=115 mg/dl and intensify further if >115 mg/dl again. A total of 20 visits within a time frame of 2 and half years will be performed. Visits procedures will include routine biochemistry, eGFR, lipids, fasting glucose, insulin and full blood count, HbA1c, SHBG, hsCRP. EPIC and G-PAQ questionnaires will be collected. Autonomic function testing using deep breathing heart rate variability, and a sensitive measure of small fiber neuropathy using corneal confocal microscopy and a 24 hour urine collection for urinary isoprostanes to measure oxidative stress will be performed, at baseline, 12 and 24 months.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus Type 2 Drug: Metformin Drug: Gliclazide Drug: Sitagliptin Drug: Liraglutide Drug: Pioglitazone Drug: Dapagliflozin Drug: human insulin Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: This is an randomized open label clinical trial.
Primary Purpose: Other
Official Title: Does Glycated Hemoglobin Variability in Type 2 Diabetes Differ Depending on the Diabetes Treatment Threshold Used in the Qatari Population: Implication on Diabetes Complication Risk?
Study Start Date : November 2016
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment arm 1

75 Type 2 diabetic patients with a gender balance who will have the intervention if/when their FBG >140mg/dl

Intervention: intensify treatment until their FBG is <90mg/dl, using whatever treatment is clinically appropriate for them using different interventions (Metformin, Gliclazide, Sitagliptin, Dapagliflozin, Liraglutide, Pioglitazone, human insulin), and only intensify it further if their FPG rises to >140mg/dl again.

Drug: Metformin
Initial: 500 mg once daily; dosage may be increased by 500 mg weekly; maximum dose: 2,000 mg once daily
Other Name: Glucophage

Drug: Gliclazide

There is no fixed-dosage regimen for the management of diabetes mellitus with gliclazide. Dose will be individualized based on frequent determinations of blood glucose during dose titration and throughout maintenance. The 30 mg modified-release tablet equals the 80 mg immediate-release tablet.

Immediate-release tablet: Initial: 80 mg twice daily; titrate based on blood glucose levels. Usual dosage range: 80 to 320 mg/day (maximum dose: 320 mg/day); dosage of ≥160 mg should be divided into 2 equal parts for twice-daily administration.

Modified-release tablet: Initial: 30 mg once daily; titrate in 30 mg increments every 2 weeks based on blood glucose levels. Maximum dose: 120 mg once daily

Other Names:
  • Diamicron
  • Diamicron MR

Drug: Sitagliptin
Oral: 100 mg once daily
Other Name: Januvia

Drug: Liraglutide
SubQ: Initial: 0.6 mg once daily for 1 week; then increase to 1.2 mg once daily; may increase further to 1.8 mg once daily if optimal glycemic response not achieved with 1.2 mg daily.
Other Name: Victoza

Drug: Pioglitazone

Oral, Monotherapy or combination therapy: 15-30 mg once daily

Patients with heart failure (NYHA Class I or II): Monotherapy or combination therapy: 15 mg once daily

Other Name: Actos

Drug: Dapagliflozin
5mg once daily increasing to 10mg once daily as required
Other Names:
  • Forxiga
  • Farxiga

Drug: human insulin
insulin dosage and administration according to physician
Other Names:
  • novorapid
  • glargine

Experimental: Treatment arm 2

75 Type 2 diabetic patients with a gender balance who will have the intervention if/when their FBG >115mg/dl

Intervention: intensify treatment until FBG is <=115 mg/dl and intensify further if >115 mg/dl again, using what ever clinical treatment is necessary (Metformin, Gliclazide, Sitagliptin, Dapagliflozin, Liraglutide, Pioglitazone, human insulin).

Drug: Metformin
Initial: 500 mg once daily; dosage may be increased by 500 mg weekly; maximum dose: 2,000 mg once daily
Other Name: Glucophage

Drug: Gliclazide

There is no fixed-dosage regimen for the management of diabetes mellitus with gliclazide. Dose will be individualized based on frequent determinations of blood glucose during dose titration and throughout maintenance. The 30 mg modified-release tablet equals the 80 mg immediate-release tablet.

Immediate-release tablet: Initial: 80 mg twice daily; titrate based on blood glucose levels. Usual dosage range: 80 to 320 mg/day (maximum dose: 320 mg/day); dosage of ≥160 mg should be divided into 2 equal parts for twice-daily administration.

Modified-release tablet: Initial: 30 mg once daily; titrate in 30 mg increments every 2 weeks based on blood glucose levels. Maximum dose: 120 mg once daily

Other Names:
  • Diamicron
  • Diamicron MR

Drug: Sitagliptin
Oral: 100 mg once daily
Other Name: Januvia

Drug: Liraglutide
SubQ: Initial: 0.6 mg once daily for 1 week; then increase to 1.2 mg once daily; may increase further to 1.8 mg once daily if optimal glycemic response not achieved with 1.2 mg daily.
Other Name: Victoza

Drug: Pioglitazone

Oral, Monotherapy or combination therapy: 15-30 mg once daily

Patients with heart failure (NYHA Class I or II): Monotherapy or combination therapy: 15 mg once daily

Other Name: Actos

Drug: Dapagliflozin
5mg once daily increasing to 10mg once daily as required
Other Names:
  • Forxiga
  • Farxiga

Drug: human insulin
insulin dosage and administration according to physician
Other Names:
  • novorapid
  • glargine




Primary Outcome Measures :
  1. Determination of the variability of HbA1c (by measurement of standard deviation of HbA1c) between the 2 diabetes treatment thresholds [ Time Frame: 24-30 months ]
    The primary objective of this study is to determine whether treatment to one of 2 threshold levels will result in one group of type 2 diabetes patients having the same mean HbA1c but with differing HbA1c variability to that of another.


Secondary Outcome Measures :
  1. Association of the variability of HbA1c (by measurement of standard deviation of HbA1c) to microvascular changes in heart rate variability, corneal nerve fiber density, albumin/creatinine ratio and estimated glomerular filtration rate. [ Time Frame: 24-30 months ]
    Heart rate variability will be measured by ECG changes to deep breathing. Corneal nerve fiber density will be measured by confocal corneal microscopy

  2. Association of the variability of HbA1c (by measurement of standard deviation of HbA1c) to oxidative stress markers measured by urinary isoprostanes and inflammation measured by highly sensitive C-reactive protein. [ Time Frame: 24-30 months ]
    This will be assessed by comparing the results of HbA1c and it's variability every 6 weeks with results of routine biochemistry including eGFR, lipids, SHBG, hsCRP measured on visit one (initial visit), visit 11 (midpoint of the study), and visit 20 (end of the study).

  3. Comparison of HbA1c (percent) for each subject at baseline and following sample storage of 2 years to assess HbA1c measurement stability. [ Time Frame: 2-3 years. ]
    HbA1c will be measured at the time of the sample collection from fresh and heamolysed blood, then the remaining of the samples will be aliquoted and stored in -80 C then remeasured again after short term storage (2-3 years)



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Qatari subjects only with type 2 diabetes taking any medication.
  • HbA1c 7.5-9.0%.
  • Body mass index 26-36.
  • Age 18 - 65 years of age.
  • Recruitment of a gender balance reflecting the local eligible diabetes patients until 150 are recruited.

Exclusion Criteria:

  • Patients with anemia or other conditions known to affect the validity of HbA1c measurement e.g. a haemoglobinopathy known to affect the Hamad HbA1c method or renal failure (CKD Stage 5)
  • Patients with concurrent illness
  • Patients on medication leading to insulin resistance e.g. corticosteroids
  • Pregnancy
  • Active retinopathy
  • Any clinical exclusion for optimal diabetes control
  • Hypoglycemic unawareness

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): NCT02879409


Contacts
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Contact: Stephen Atkin, MD PhD +974 44928263 ext 00974 sla2002@qatar-med.cornell.edu

Locations
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Qatar
Hamad Medical Corporation Recruiting
Doha, Qatar, 3050
Contact: Ibrahim Janahi, MD    4439-2434 ext 00974    Imohd@hamad.qa   
Principal Investigator: Ibrahim Janahi, MD         
Sub-Investigator: Mashhood Siddique, MD         
Sub-Investigator: Hamda Ali, MD         
Sponsors and Collaborators
Weill Cornell Medical College in Qatar
Hamad Medical Corporation
Sidra Medical and Research Center
University of Hull
Investigators
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Principal Investigator: Stephen Atkin, MD PhD Weill Cornell Medicine in Qatar

Additional Information:
Publications:

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Responsible Party: Weill Cornell Medical College in Qatar
ClinicalTrials.gov Identifier: NCT02879409     History of Changes
Other Study ID Numbers: 14-00058
NPRP: 8-315-3-065 ( Other Grant/Funding Number: Qatar National Research Fund )
14-00058 ( Other Identifier: Weill Cornell Medical College in Qatar )
15103/15 ( Other Identifier: Hamad Medical Corporation )
First Posted: August 25, 2016    Key Record Dates
Last Update Posted: June 2, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Weill Cornell Medical College in Qatar:
HbA1c variability
Diabetes Mellitus Type 2
Diabetes microvascular complications
Diabetes macrovascular complications
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Insulin, Globin Zinc
Metformin
Sitagliptin Phosphate
Pioglitazone
Liraglutide
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Gliclazide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Sodium-Glucose Transporter 2 Inhibitors