SITACLAMP: Sitagliptin and Glucagon Counterregulation

• Sponsor: Lund University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02256189
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 28
• Location: 1
• Arms: 2
• Actual Duration (Months): 26
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

To evaluate the effect of DPP-4 inhibition on glucagon counter-regulatory mechanisms at moderate hypoglycemia in metformin-treated subjects with T2DM

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Sitagliptin; Drug: Placebo	Phase 4

Detailed Description

The glucagon response to mild (3.0 mmol/l) hypoglycemia with and without DPP-4 inhibition by sitagliptin will be evaluated in elderly subjects with metformin treated type 2 diabetes to explore whether DPP-4 inhibition affects glucagon counter-regulation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: The Effect of Sitagliptin on Glucagon Counterregulation and Incretin Hormones During Mild Hypoglycemia in Elderly Patients With Metformin-treated Type 2 Diabetes
• Actual Study Start Date: Apr 1, 2015
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: Sitagliptin first, then placebo Sitagliptin treatment for four weeks, then washout for four weeks, then placebo for four weeks	Drug: Sitagliptin; Sitagliptin 100 mg daily
Other: Placebo first, then sitagliptin Placebo for four weeks, then washout for four weeks, then sitagliptin for four weeks	Drug: Placebo; Placebo one tablet daily

Outcome Measures

Primary Outcome Measures

1. Glucagon Counterregulation to Hypoglycemia [Four weeks treatment]

   Change in plasma glucagon to insulin-induced hypoglycemia after four weeks of treatment with sitagliptin and placebo

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Written consent has been given.

2. Patients with metformin treated T2DM (metformin dose >0,5 g/day and stable during the preceding 3 months)

3. Age >65 years.

4. HbA1c 6.0-8.5% (43-67 mmol/mol; inclusive) at visit 1.

5. Ability to complete the study

Exclusion Criteria:

1. A history of any secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly.

2. Type 2 diabetes, positive GAD antibodies

3. eGFR <60 ml/min

4. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1

5. Any history of recent (<2 weeks) recurrent or severe hypoglycemic episodes.

6. Liver disease such as cirrhosis or chronic active hepatitis

7. History of coronary heart disease or heart failure class III or IV

8. Donation of one unit (500 ml) or more of blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks.

9. Treatment with growth hormone of chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1.

10. Use of other investigational drugs at visit 1 or within 30 days of visit 1, unsuitable for the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Skane University Hospital Malmö	Malmö		Sweden	20502

Sponsors and Collaborators

• Lund University
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Bo Ahrén, MD, PhD, Lund University

Study Documents (Full-Text)

• Study Protocol - Dec 12, 2015
• Statistical Analysis Plan - Dec 12, 2015

More Information

Publications

None provided.

• Responsible Party: Bo Ahren, Professor, Lund University
• ClinicalTrials.gov Identifier: NCT02256189
• Other Study ID Numbers: 300A
• First Posted: Oct 3, 2014
• Last Update Posted: Feb 20, 2019
• Last Verified: Oct 1, 2018

• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Sitagliptin Phosphate

Study Results

Participant Flow

Arm/Group Title	Sitagliptin First, Then Placebo	Placebo First, Then Sitagliptin
Arm/Group Description	Sitagliptin first for four weeks, then washout for four weeks, then placebo for four weeks	Placebo first for four weeks, then washout for four weeks, then placebo for four weeks
Period Title: Overall Study
STARTED	15	13
COMPLETED	15	13
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sitagliptin First, Then Placebo	Placebo First, Then Stagliptin	Total
Arm/Group Description	Hypoglycemia clamp with sitagliptin Sitagliptin: Treatment with sitagliptin 100mg QD for four weeks followed by hyperinsulinemic hypoglycemic clamp	Hypoglycemia clamp with placebo Placebo: Treatment with placebo QD for four weeks followed by hyperinsulinemic hypoglycemic clamp	Total of all reporting groups
Overall Participants	15	13	28
Age, Customized (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	75.0 (5.9)	71.9 (5.7)	73.6 (5.9)
Sex: Female, Male (Count of Participants)
Female	7 46.7%	5 38.5%	12 42.9%
Male	8 53.3%	8 61.5%	16 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	15 100%	13 100%	28 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Sweden	15 100%	13 100%	28 100%
Fasting glucagon (pmol/l) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pmol/l]	29.5 (9.7)	30.0 (12.2)	29.8 (10.9)

Outcome Measures

1. Primary Outcome

Title	Glucagon Counterregulation to Hypoglycemia
Description	Change in plasma glucagon to insulin-induced hypoglycemia after four weeks of treatment with sitagliptin and placebo
Time Frame	Four weeks treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sitagliptin	Placebo
Arm/Group Description	Hypoglycemia clamp with sitagliptin Sitagliptin: Treatment with sitagliptin 100mg QD for four weeks followed by hyperinsulinemic hypoglycemic clamp	Hypoglycemia clamp with placebo Placebo: Treatment with placebo QD for four weeks followed by hyperinsulinemic hypoglycemic clamp
Measure Participants	28	28
Mean (Standard Error) [pmol/l]	16.0 (2.9)	16.5 (2.8)

Adverse Events

Time Frame	4 weeks
Arm/Group Title	Sitagliptin First, Then Placebo		Placebo First, Then Stagliptin		Sitagliptin		Placebo
Arm/Group Description	Sitagliptin first for four weeks, then washout for four weeks, then placebo for four weeks		Placebo first for four weeks, then washout for four weeks, then sitalgiptin for four weeks		Sitagliptin 100mg Daily for four weeks, either before or after a 4 week placebo period		Placebo Daily for four weeks, efter before or after a 4 week sitagliptin period
All Cause Mortality
	Sitagliptin First, Then Placebo		Placebo First, Then Stagliptin		Sitagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/13 (0%)		0/28 (0%)		0/28 (0%)
Serious Adverse Events
	Sitagliptin First, Then Placebo		Placebo First, Then Stagliptin		Sitagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/13 (0%)		0/28 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Sitagliptin First, Then Placebo		Placebo First, Then Stagliptin		Sitagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/13 (0%)		0/28 (0%)		0/28 (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.