Trial Outcomes & Findings for Dipeptidyl Peptidase-4 Inhibitors and Alpha-cell Recovery (NCT NCT01272583)

NCT ID: NCT01272583

Last Updated: 2014-03-14

Results Overview

Change in glucagon concentration from the initialisation phase to 40 minutes after occurrence of the autonomic reaction to hypoglycaemia

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

16 participants

Primary outcome timeframe

Change from initialisation phase to 40 minutes after onset of hypoglycaemia

Results posted on

2014-03-14

Participant Flow

Participants came to the Academic Medical Center in Amsterdam for a screening visit to determine eligibility for the study.

Patients were excluded if they were found to have impaired awareness of hypoglycaemia, had a history of seizures, cardiac arrhythmia (or used beta-adrenoreceptor blockers) and/or acute infection in the 12 weeks before the study, or evidence of severe diabetes complications (autonomic neuropathy, nephropathy or proliferative retinopathy).

Participant milestones

Participant milestones
Measure
Sequence A (Sitagliptin→Placebo)
Cross-over, both arms reveived the same intervention in different order. Sitagliptin : 100 mg once daily for six weeks Placebo : placebo, once daily for six weeks
Sequence B (Placebo→Sitagliptin)
Cross-over, both arms reveived the same intervention in different order. Sitagliptin : 100 mg once daily for six weeks Placebo : placebo, once daily for six weeks
Overall Study
STARTED
8
8
Overall Study
COMPLETED
8
8
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dipeptidyl Peptidase-4 Inhibitors and Alpha-cell Recovery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Sequence A (Sitagliptin→Placebo)
n=8 Participants
Cross-over, both arms reveived the same intervention in different order. Sitagliptin : 100 mg once daily for six weeks Placebo : placebo, once daily for six weeks
Sequence B (Placebo→Sitagliptin)
n=8 Participants
Cross-over, both arms reveived the same intervention in different order. Sitagliptin : 100 mg once daily for six weeks Placebo : placebo, once daily for six weeks
Total
n=16 Participants
Total of all reporting groups
Age, Continuous
30.5 years
INTER_QUARTILE_RANGE 26.3-39 • n=99 Participants
33.5 years
INTER_QUARTILE_RANGE 27.8-40.8 • n=107 Participants
31.5 years
INTER_QUARTILE_RANGE 27.0-40.0 • n=206 Participants
Sex: Female, Male
Female
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Sex: Female, Male
Male
8 Participants
n=99 Participants
8 Participants
n=107 Participants
16 Participants
n=206 Participants
Region of Enrollment
Netherlands
8 participants
n=99 Participants
8 participants
n=107 Participants
16 participants
n=206 Participants

PRIMARY outcome

Timeframe: Change from initialisation phase to 40 minutes after onset of hypoglycaemia

Change in glucagon concentration from the initialisation phase to 40 minutes after occurrence of the autonomic reaction to hypoglycaemia

Outcome measures

Outcome measures
Measure
Baseline
n=16 Participants
Sitagliptin Treatment
n=16 Participants
Placebo
n=16 Participants
Glucagon Response to Acute Hypoglycaemia
1.33 pmol/L
Interval -0.67 to 2.67
1.0 pmol/L
Interval -0.67 to 2.67
1.33 pmol/L
Interval -1.0 to 2.33

PRIMARY outcome

Timeframe: 0, 10, 20 and 40 minutes

Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.

Outcome measures

Outcome measures
Measure
Baseline
n=16 Participants
Sitagliptin Treatment
n=16 Participants
Placebo
n=16 Participants
Glucagon Response to Acute Hypoglycaemia
120 pmol*minutes/L
Interval 90.0 to 215.0
125 pmol*minutes/L
Interval 20.0 to 215.0
120 pmol*minutes/L
Interval 85.0 to 200.0

SECONDARY outcome

Timeframe: 0, 10, 20, 40 minutes

Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.

Outcome measures

Outcome measures
Measure
Baseline
n=16 Participants
Sitagliptin Treatment
n=16 Participants
Placebo
n=16 Participants
Intact and Total Glucagon Like Peptide-1 (GLP-1), Intact and Total Gastric Inhibitory Peptide (GIP) Response to Acute Hypoglycaemia
GIP total
302.5 pmol*minutes/L
Interval 201.3 to 436.3
285.0 pmol*minutes/L
Interval 160.0 to 367.5
342.5 pmol*minutes/L
Interval 238.8 to 497.5
Intact and Total Glucagon Like Peptide-1 (GLP-1), Intact and Total Gastric Inhibitory Peptide (GIP) Response to Acute Hypoglycaemia
GLP-1 intact
2.000 pmol*minutes/L
Interval 0.0 to 15.5
43.50 pmol*minutes/L
Interval 12.0 to 81.5
4.500 pmol*minutes/L
Interval 0.0 to 21.0
Intact and Total Glucagon Like Peptide-1 (GLP-1), Intact and Total Gastric Inhibitory Peptide (GIP) Response to Acute Hypoglycaemia
GLP-1 total
562.2 pmol*minutes/L
Interval 435.0 to 623.8
555.0 pmol*minutes/L
Interval 450.0 to 611.3
552.5 pmol*minutes/L
Interval 433.8 to 596.3
Intact and Total Glucagon Like Peptide-1 (GLP-1), Intact and Total Gastric Inhibitory Peptide (GIP) Response to Acute Hypoglycaemia
GIP intact
455.0 pmol*minutes/L
Interval 361.3 to 513.8
490.0 pmol*minutes/L
Interval 461.3 to 630.0
452.5 pmol*minutes/L
Interval 435.0 to 532.5

SECONDARY outcome

Timeframe: 0, 10, 20, 40 minutes

Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.

Outcome measures

Outcome measures
Measure
Baseline
n=16 Participants
Sitagliptin Treatment
n=16 Participants
Placebo
n=16 Participants
Epinephrine Response to Acute Hypoglycaemia
36.1 nmol*minutes/L
Interval 31.1 to 62.5
32.6 nmol*minutes/L
Interval 17.0 to 65.0
58.7 nmol*minutes/L
Interval 34.8 to 71.3

SECONDARY outcome

Timeframe: 0, 10, 20, 40 minutes

Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.

Outcome measures

Outcome measures
Measure
Baseline
n=16 Participants
Sitagliptin Treatment
n=16 Participants
Placebo
n=16 Participants
Norepinephrine Response to Acute Hypoglycaemia
70.0 nmol*minutes/L
Interval 52.5 to 88.1
62.5 nmol*minutes/L
Interval 44.9 to 73.0
62.3 nmol*minutes/L
Interval 49.1 to 72.5

SECONDARY outcome

Timeframe: 0, 10, 20, 40 minutes

Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.

Outcome measures

Outcome measures
Measure
Baseline
n=16 Participants
Sitagliptin Treatment
n=16 Participants
Placebo
n=16 Participants
Growth Hormone Response to Acute Hypoglycaemia
1299 mU*minutes/L
Interval 313.5 to 2560.0
261.5 mU*minutes/L
Interval 47.0 to 1499.0
1406 mU*minutes/L
Interval 781.0 to 2626.0

SECONDARY outcome

Timeframe: 0, 10, 20, 40 minutes

Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.

Outcome measures

Outcome measures
Measure
Baseline
n=16 Participants
Sitagliptin Treatment
n=16 Participants
Placebo
n=16 Participants
Cortisol Response to Acute Hypoglycaemia
14480 mU*minutes/L
Interval 11300.0 to 17180.0
13190 mU*minutes/L
Interval 10920.0 to 18680.0
14800 mU*minutes/L
Interval 8985.0 to 19160.0

SECONDARY outcome

Timeframe: Change from baseline symptomatic response at hypoglycaemia and 30 minutes after hypoglycaemia

The symptomatic responses to hypoglycaemia were assessed using a standard validated symptom questionnaire adapted for experimental hypoglycaemia (McCrimmon et al (2003) Diabet.Med. 20: 507-509). A 7-point Likert scale (1=symptom absent; 7=symptom experienced with great intensity) was used to score presence and intensity of autonomic and neuroglycopenic symptoms of hypoglycaemia. Symptom scores were obtained during the initialisation phase, at occurrence of autonomic reaction and again 30 minutes later. For analyses the scale was considered as a continuous variable.

Outcome measures

Outcome measures
Measure
Baseline
n=16 Participants
Sitagliptin Treatment
n=16 Participants
Placebo
n=16 Participants
Symptomatic Hormone Responses to Acute Hypoglycaemia.
Autonomic symptoms score
1.7 units on a scale
Interval 1.7 to 2.9
1.3 units on a scale
Interval 1.0 to 2.6
1.5 units on a scale
Interval 1.0 to 2.2
Symptomatic Hormone Responses to Acute Hypoglycaemia.
Neurologic symptoms score
2.1 units on a scale
Interval 1.7 to 3.4
2.4 units on a scale
Interval 1.7 to 3.8
2.1 units on a scale
Interval 1.5 to 3.3

Adverse Events

Baseline

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Sitagliptin Treatment

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Josefine E. Schopman

Academic Medical Center

Phone: +31 20 5669111

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60