Incretins in Impaired Fasting Glucose

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00364377
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

People with high fasting glucose can develop type 2 diabetes with the passage of time. This study is being done to determine the effect of a novel medication in people with this elevated fasting glucose. Sitagliptin is a substance that raises levels of a hormone normally found in the blood. This hormone, called glucagon-like peptide-1 (GLP-1), is normally released by the intestine in response to the presence of food. This hormone acts like a messenger between the intestine and the pancreas to raise insulin levels, and therefore, lower blood sugars. Sitagliptin is effective in people with diabetes, however, this study is being done to determine if Sitagliptin is effective in people with high fasting glucose who do not yet have diabetes.

Condition or Disease	Intervention/Treatment	Phase
Pre-diabetes	Drug: Sitagliptin; Other: Placebo	Phase 4

Detailed Description

Impaired fasting glucose (IFG) confers a high risk of progression to diabetes. Its pathogenesis has been an area of active investigation, with defects in insulin and glucagon secretion as well as insulin action likely to play a role. Several studies have suggested that the prediabetic and diabetic state are associated with alterations in circulating incretin concentrations. More recently, a large study of non-diabetic individuals demonstrated decreased GLP-1 concentrations after a glucose challenge in individuals with prediabetes but concluded that defects in GLP-1 secretion were unrelated to insulin secretion. In impaired glucose tolerance (IGT), defects in incretin-induced insulin secretion coexist with defects in glucose induced insulin secretion.

Worsening degrees of glucose tolerance are associated with decreased insulin secretion for the prevailing insulin action. Moreover early glucagon suppression is impaired in IGT. Since GLP-1 is an insulin secretagogue and suppresses glucagon, it is conceivable that defects in GLP-1 secretion could contribute to the pathogenesis of pre-diabetes. Inhibition of Dipeptidyl Peptidase-4 (DPP-4), an enzyme which rapidly degrades the incretin hormones, has been shown to be a useful therapeutic strategy in type 2 diabetes. DPP-4 inhibitors increase (model-calculated) insulin secretion and decrease glucagon concentrations resulting in a lowering of fasting (and postprandial) glucose concentrations in people with type 2 diabetes. Their effects in people with IFG are less certain. However, DPP-4 inhibitors provide an opportunity to directly examine the contribution of abnormal incretin concentrations to the pathogenesis of IFG, by raising concentrations of endogenous incretin hormones.

The current experiments tested this hypothesis by measuring insulin secretion and action and fasting and postprandial glucose turnover before and after 8 weeks of therapy with a DPP-4 inhibitor.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Role of Incretins in the Pathogenesis of Fasting and Postprandial Glucose Metabolism in People With Impaired Fasting Glucose
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sitagliptin People with impaired fasting glucose randomized to treatment with sitagliptin 100 mg once daily.	Drug: Sitagliptin; 100 mg once daily; Other Names: Januvia
Placebo Comparator: Placebo People with impaired fasting glucose randomized to treatment with placebo once daily.	Other: Placebo; once daily for duration of the study

Outcome Measures

Primary Outcome Measures

1. Lowering of Fasting Glucose [8 weeks]

   fasting glucose taken as the mean of blood glucose measured at -30, -20, -10 and 0 minutes prior to each inpatient meal study

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Twenty four participants aged 35 to 70 years with impaired fasting glucose (100mg/dl-125 mg/dl) will be studied.

Inclusion Criteria:

• Males and females between the ages of 35-70.

• Good health as determined by past medical history,physical examination, vital signs, electrocardiogram and laboratory tests at the time of screening.

• Patients on diuretics or thyroid hormone therapy must be on a stable dose (at least 3 months prior to screening) and the maintenance dose may not be adjusted during the study.

Exclusion Criteria:

• Individuals with a body mass index less than 19 or greater than 40 kg/m^2, or a total weight > 130 kg, will be excluded from study.

• Subjects less than 35 years will not be studied in order to minimize the possibility of studying subjects with type 1 diabetes.

• No history of a) significant nephropathy, (i.e., plasma creatinine > 1.4 mg/dl in women and 1.5 mg/dl in men, and/or proteinuria); b) clinically significant atherosclerotic vascular disease (e.g., history of heart attack or angina); c) a known systemic illness.

• Pregnant or lactating females.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Adrian Vella, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Adrian Vella, Professor of medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00364377
• Other Study ID Numbers: 06-002673
• First Posted: Aug 15, 2006
• Last Update Posted: Dec 6, 2011
• Last Verified: Nov 1, 2011

• Additional relevant MeSH terms: Prediabetic State; Sitagliptin Phosphate

Study Results

Participant Flow

Recruitment Details	Impaired Fasting Glucose (IFG) not on treatment with glucose-lowering medication

Arm/Group Title	Sitagliptin	Placebo
Arm/Group Description	People with impaired fasting glucose treated with sitagliptin 100mg once daily.	People with impaired fasting glucose treated with placebo once daily.
Period Title: Overall Study
STARTED	11	11
COMPLETED	11	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sitagliptin	Placebo	Total
Arm/Group Description	People with impaired fasting glucose treated with sitagliptin 100mg once daily.	People with impaired fasting glucose treated with placebo once daily.	Total of all reporting groups
Overall Participants	11	11	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.2 (2.5)	54.1 (2.4)	54.7 (1.8)
Sex: Female, Male (Count of Participants)
Female	10 90.9%	8 72.7%	18 81.8%
Male	1 9.1%	3 27.3%	4 18.2%
Region of Enrollment (participants) [Number]
United States	11 100%	11 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Lowering of Fasting Glucose
Description	fasting glucose taken as the mean of blood glucose measured at -30, -20, -10 and 0 minutes prior to each inpatient meal study
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Analysis was per protocol - all participants completed the intervention

Arm/Group Title	Sitagliptin	Placebo
Arm/Group Description	People with impaired fasting glucose treated with sitagliptin 100mg once daily.	People with impaired fasting glucose treated with placebo once daily.
Measure Participants	11	11
Mean (Standard Error) [mmol/l]	5.78 (0.12)	5.83 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin, Placebo
	Comments	Paired comparisons (within groups) to examine differences between the baseline study and after 8-weeks of treatment were made using Student's two-tailed t-test for paired samples. Between-group comparisons were made using Student's two-tailed t-test for unpaired samples. Given the previously observed variation in fasting glucose
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Twelve weeks
Arm/Group Title	Sitagliptin		Placebo
Arm/Group Description	People with impaired fasting glucose treated with sitagliptin 100mg once daily.		People with impaired fasting glucose treated with placebo once daily.
All Cause Mortality
	Sitagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sitagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Sitagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)
Skin and subcutaneous tissue disorders
Rash	0/11 (0%)	0	0/11 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.