Trial Outcomes & Findings for Ghrelin Dose Finding In Frail Elderly (NCT NCT01605435)

Results Overview

Number and type of treatment emergent adverse events

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

30 days following the last administration of study treatment.

Results posted on

2019-12-12

Participant Flow

Study participants were recruited from community dwelling adults meeting study criteria expressing interest in participating in research studies at University of Pennsylvania.

Dose finding with each participant receiving placebo at their first study visits and three escalating doses of ghrelin, separated by 3-7 days in visits 2,3 and 4.

Participant milestones

Participant milestones
Measure	Initial Dosing Group Visit 1: Placebo Visit 2: 2 ug/kg ghrelin Visit 3: 5 ug/kg ghrelin Visit 4: 10 ug/kg ghrelin	Second Dosing Group Visit 1: Placebo Visit 2: 5 ug/kg ghrelin Visit 3: 7.5 ug/kg ghrelin Visit 4: 10 ug/kg ghrelin
Overall Study STARTED	2	3
Overall Study COMPLETED	2	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ghrelin Dose Finding In Frail Elderly

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ghrelin n=5 Participants Dose finding with each participant receiving placebo and three doses of ghrelin, separated by 3-7 days Ghrelin: The first three participants will receive 2 mcg/kg as a single subcutaneous dose at Visit 3, 5 mcg/kg as a single subcutaneous dose at Visit 4, and 10 mcg/Kg as a single subcutaneous dose at visit 5. There will be 3-10 days between visits. The next three participants will receive either the same dosing at the first three, a regimen that includes an intermediate dose (e.g., 7.5 mcg/kg), or higher (e.g., 12, 15, and 18 mcg/kg) doses.
Age, Continuous	85 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants

PRIMARY outcome

Timeframe: 30 days following the last administration of study treatment.

Population: At the first visit all participants received s.c. placebo. The first two participants received 2 ,5, and 10ug/kg of ghrelin at visit 2,3 and 4 consecutively. The final three participants received 5,7.5, and 10ug/kg of s.c. ghrelin at visits 2,3 and 4 consecutively.

Number and type of treatment emergent adverse events

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants All 5 subjects received s.c. placebo at visit 1.	5ug/kg n=5 Participants The first two participants received 5ug/kg of s.c. ghrelin at visit 3. The final three participants received 5ug/kg of s.c. ghrelin at visits 2.	7.5ug/kg n=3 Participants The final three participants received 7.5ug/kg of s.c. ghrelin at visit 3.	10ug/kg n=5 Participants The first two participants received 10ug/kg of s.c. ghrelin at visit 4. The final three participants received 10ug/kg of s.c. ghrelin at visit 4.
Treatment Emergent Adverse Events burping	1 Events	1 Events	0 Events	0 Events
Treatment Emergent Adverse Events sensation of warmth	0 Events	0 Events	2 Events	1 Events
Treatment Emergent Adverse Events bristley feeling	1 Events	0 Events	0 Events	0 Events
Treatment Emergent Adverse Events dizzy	0 Events	0 Events	1 Events	0 Events
Treatment Emergent Adverse Events awareness of old incision	0 Events	0 Events	1 Events	0 Events
Treatment Emergent Adverse Events euphoria	0 Events	0 Events	0 Events	1 Events

PRIMARY outcome

Timeframe: 30 mins post-ghrelin or placebo

Population: At the first visit all participants received s.c. placebo. The first two participants received 2 ,5, and 10ug/kg of ghrelin at visit 2, 3 and 4 consecutively. The final three participants received 5,7.5, and 10ug/kg of s.c. ghrelin at visits 2,3 and 4 consecutively.

Median energy intake at breakfast, which was served 30 minutes post-placebo or ghrelin administration demonstrated at each dose level.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants All 5 subjects received s.c. placebo at visit 1.	2ug/kg n=2 Participants The first two participants received 2ug/kg of s.c. ghrelin at visit 2.	5ug/kg n=5 Participants The first two participants received 5ug/kg of s.c. ghrelin at visit 3. The final three participants received 5ug/kg of s.c. ghrelin at visits 2.	7.5ug/kg n=3 Participants The final three participants received 7.5ug/kg of s.c. ghrelin at visit 3.	10ug/kg n=5 Participants The first two participants received 10ug/kg of s.c. ghrelin at visit 4. The final three participants received 10ug/kg of s.c. ghrelin at visit 4.
Median Energy Intake	535.16 Kilocalories Interval 482.14 to 670.05	578 Kilocalories Interval 436.28 to 719.872	813 Kilocalories Interval 500.87 to 1083.75	852 Kilocalories Interval 790.26 to 917.69	862.04 Kilocalories Interval 493.34 to 925.91

PRIMARY outcome

Timeframe: 30 mins post-ghrelin or placebo

Population: At the first visit all participants received s.c. placebo. The first two participants received 2 ,5, and 10ug/kg of ghrelin at visit 2,3 and 4 consecutively. The final three participants received 5,7.5, and 10ug/kg of s.c. ghrelin at visits 2,3 and 4 consecutively.

% of total energy relative to placebo - breakfast served 30 minutes post-placebo or ghrelin administration.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants All 5 subjects received s.c. placebo at visit 1.	2ug/kg n=2 Participants The first two participants received 2ug/kg of s.c. ghrelin at visit 2.	5ug/kg n=5 Participants The first two participants received 5ug/kg of s.c. ghrelin at visit 3. The final three participants received 5ug/kg of s.c. ghrelin at visits 2.	7.5ug/kg n=3 Participants The final three participants received 7.5ug/kg of s.c. ghrelin at visit 3.	10ug/kg n=5 Participants The first two participants received 10ug/kg of s.c. ghrelin at visit 4. The final three participants received 10ug/kg of s.c. ghrelin at visit 4.
Percentage of Total Energy Intake Relative to Placebo	100 percentage of placebo intake	110 percentage of placebo intake	135 percentage of placebo intake	139 percentage of placebo intake	129 percentage of placebo intake

PRIMARY outcome

Timeframe: 30 minutes after ghrelin administration

Population: At the first visit all participants received s.c. placebo. The first two participants received 2 ,5, and 10ug/kg of ghrelin at visit 2,3 and 4 consecutively. The final three participants received 5,7.5, and 10ug/kg of s.c. ghrelin at visits 2,3 and 4 consecutively.

median growth hormone peak 30 minutes after placebo/ghrelin.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants All 5 subjects received s.c. placebo at visit 1.	2ug/kg n=2 Participants The first two participants received 2ug/kg of s.c. ghrelin at visit 2.	5ug/kg n=5 Participants The first two participants received 5ug/kg of s.c. ghrelin at visit 3. The final three participants received 5ug/kg of s.c. ghrelin at visits 2.	7.5ug/kg n=3 Participants The final three participants received 7.5ug/kg of s.c. ghrelin at visit 3.	10ug/kg n=5 Participants The first two participants received 10ug/kg of s.c. ghrelin at visit 4. The final three participants received 10ug/kg of s.c. ghrelin at visit 4.
Growth Hormone	3.71 ng/mL Interval 2.52 to 5.91	16.87 ng/mL Interval 4.27 to 29.47	31.81 ng/mL Interval 7.85 to 50.0	39.20 ng/mL Interval 12.2 to 39.21	33.63 ng/mL Interval 4.99 to 50.0

PRIMARY outcome

Timeframe: 0, 60 and 120 minutes after dosing

Population: At the first visit all participants received s.c. placebo. The first two participants received 2 ,5, and 10ug/kg of ghrelin at visit 2,3 and 4 consecutively. The final three participants received 5,7.5, and 10ug/kg of s.c. ghrelin at visits 2,3 and 4 consecutively.

Cortisol response to ghrelin or placebo - levels at 0, 60 and 120 minutes after dosing

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants All 5 subjects received s.c. placebo at visit 1.	2ug/kg n=2 Participants The first two participants received 2ug/kg of s.c. ghrelin at visit 2.	5ug/kg n=5 Participants The first two participants received 5ug/kg of s.c. ghrelin at visit 3. The final three participants received 5ug/kg of s.c. ghrelin at visits 2.	7.5ug/kg n=3 Participants The final three participants received 7.5ug/kg of s.c. ghrelin at visit 3.	10ug/kg n=5 Participants The first two participants received 10ug/kg of s.c. ghrelin at visit 4. The final three participants received 10ug/kg of s.c. ghrelin at visit 4.
Cortisol Level 0 minutes, baseline	26.4 mcg/dL Interval 19.3 to 35.2	27.1 mcg/dL Interval 24.5 to 29.7	28.4 mcg/dL Interval 20.6 to 30.4	21.5 mcg/dL Interval 20.7 to 28.6	22.7 mcg/dL Interval 20.0 to 30.9
Cortisol Level 60 minutes after dosing	18.6 mcg/dL Interval 14.7 to 22.6	22.0 mcg/dL Interval 21.2 to 22.8	35.3 mcg/dL Interval 18.4 to 42.7	33.7 mcg/dL Interval 16.2 to 36.0	31.8 mcg/dL Interval 18.2 to 41.1
Cortisol Level 120 minutes after dosing	18.8 mcg/dL Interval 16.8 to 32.8	29.7 mcg/dL Interval 29.0 to 30.4	27.5 mcg/dL Interval 19.0 to 37.7	32.5 mcg/dL Interval 17.9 to 33.0	26.4 mcg/dL Interval 20.5 to 30.9

PRIMARY outcome

Timeframe: 0 minutes (baseline) and 60 or 90 minutes from dosing

Population: At the first visit all participants received s.c. placebo. The first two participants received 2 ,5, and 10ug/kg of ghrelin at visit 2,3 and 4 consecutively. The final three participants received 5,7.5, and 10ug/kg of s.c. ghrelin at visits 2,3 and 4 consecutively.

Median fasting and peak postprandial Glucose levels (60 or 90 minutes from dosing) at placebo and at each ghrelin dose.

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants All 5 subjects received s.c. placebo at visit 1.	2ug/kg n=2 Participants The first two participants received 2ug/kg of s.c. ghrelin at visit 2.	5ug/kg n=5 Participants The first two participants received 5ug/kg of s.c. ghrelin at visit 3. The final three participants received 5ug/kg of s.c. ghrelin at visits 2.	7.5ug/kg n=3 Participants The final three participants received 7.5ug/kg of s.c. ghrelin at visit 3.	10ug/kg n=5 Participants The first two participants received 10ug/kg of s.c. ghrelin at visit 4. The final three participants received 10ug/kg of s.c. ghrelin at visit 4.
Glucose Levels Fasting (0 minutes)	93 mg/dL Interval 89.0 to 122.0	90 mg/dL Interval 87.0 to 93.0	91 mg/dL Interval 88.0 to 102.0	104 mg/dL Interval 89.0 to 113.0	94 mg/dL Interval 88.0 to 106.0
Glucose Levels peak postprandial (60 or 90 minutes after dosing)	142 mg/dL Interval 125.0 to 166.0	141 mg/dL Interval 135.0 to 146.0	162 mg/dL Interval 145.0 to 187.0	167 mg/dL Interval 147.0 to 196.0	164 mg/dL Interval 153.0 to 184.0

PRIMARY outcome

Timeframe: 0 and 90 minutes after dosing

Population: At the first visit all participants received s.c. placebo. The first two participants received 2 ,5, and 10ug/kg of ghrelin at visit 2,3 and 4 consecutively. The final three participants received 5,7.5, and 10ug/kg of s.c. ghrelin at visits 2,3 and 4 consecutively.

Median fasting insulin levels at baseline and 90 minutes after dosing

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants All 5 subjects received s.c. placebo at visit 1.	2ug/kg n=2 Participants The first two participants received 2ug/kg of s.c. ghrelin at visit 2.	5ug/kg n=5 Participants The first two participants received 5ug/kg of s.c. ghrelin at visit 3. The final three participants received 5ug/kg of s.c. ghrelin at visits 2.	7.5ug/kg n=3 Participants The final three participants received 7.5ug/kg of s.c. ghrelin at visit 3.	10ug/kg n=5 Participants The first two participants received 10ug/kg of s.c. ghrelin at visit 4. The final three participants received 10ug/kg of s.c. ghrelin at visit 4.
Insulin Level Fasting (0 minutes)	12.9 uIU/mL Interval 2.0 to 16.0	14.8 uIU/mL Interval 13.0 to 16.5	8.5 uIU/mL Interval 3.1 to 16.0	8.7 uIU/mL Interval 7.0 to 17.2	9.7 uIU/mL Interval 4.7 to 16.9
Insulin Level 90 minutes after dosing	82.9 uIU/mL Interval 12.9 to 164.5	115.8 uIU/mL Interval 76.5 to 155.0	109.5 uIU/mL Interval 60.1 to 186.5	77.6 uIU/mL Interval 38.9 to 149.0	85.8 uIU/mL Interval 38.8 to 186.5

PRIMARY outcome

Timeframe: 90 and 120 minutes after dosing

Population: At the first visit all participants received s.c. placebo. The first two participants received 2 ,5, and 10ug/kg of ghrelin at visit 2,3 and 4 consecutively. The final three participants received 5,7.5, and 10ug/kg of s.c. ghrelin at visits 2,3 and 4 consecutively.

Free Fatty Acid levels (mEq/L) at 60 and 90 minutes after meal (90 and 120 minutes)

Outcome measures

Outcome measures
Measure	Placebo n=5 Participants All 5 subjects received s.c. placebo at visit 1.	2ug/kg n=2 Participants The first two participants received 2ug/kg of s.c. ghrelin at visit 2.	5ug/kg n=5 Participants The first two participants received 5ug/kg of s.c. ghrelin at visit 3. The final three participants received 5ug/kg of s.c. ghrelin at visits 2.	7.5ug/kg n=3 Participants The final three participants received 7.5ug/kg of s.c. ghrelin at visit 3.	10ug/kg n=5 Participants The first two participants received 10ug/kg of s.c. ghrelin at visit 4. The final three participants received 10ug/kg of s.c. ghrelin at visit 4.
Free Fatty Acid Level 90 minutes	0.17 mEq/L Interval 0.12 to 0.35	0.11 mEq/L Interval 0.1 to 0.12	0.22 mEq/L Interval 0.09 to 0.42	0.35 mEq/L Interval 0.2 to 0.46	0.29 mEq/L Interval 0.08 to 0.36
Free Fatty Acid Level 120 minutes	0.10 mEq/L Interval 0.06 to 0.12	0.08 mEq/L Interval 0.05 to 0.11	0.09 mEq/L Interval 0.04 to 0.27	0.14 mEq/L Interval 0.11 to 0.15	0.12 mEq/L Interval 0.06 to 0.14

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

2mcg/kg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

5mcg/kg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

7.5mcg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

10mcg/kg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=5 participants at risk Visit 1 for all five subjects placebo injected s.c. at time 0	2mcg/kg n=2 participants at risk Visit 2 for the first two subjects 2mcg/kg ghrelin injected s.c at time 0	5mcg/kg n=5 participants at risk Visit 3 for the first two subjects Visit 2 for the last three subjects 5mcg/kg ghrelin injected s.c. at time 0	7.5mcg/kg n=3 participants at risk Visit 3 for the last three subjects 7.5mcg/kg ghrelin injected at time 0	10mcg/kg n=5 participants at risk Visit 4 for all five subjects
General disorders euphoria	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/2 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/3 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	20.0% 1/5 • Number of events 1 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.
General disorders bristley feeling in chest	20.0% 1/5 • Number of events 1 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/2 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/3 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.
Skin and subcutaneous tissue disorders awareness of sternotomy incision	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/2 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	33.3% 1/3 • Number of events 1 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.
Nervous system disorders dizziness	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/2 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	33.3% 1/3 • Number of events 1 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.
Gastrointestinal disorders burping	20.0% 1/5 • Number of events 1 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/2 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	20.0% 1/5 • Number of events 1 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/3 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.
General disorders warmth	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/2 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	0.00% 0/5 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	66.7% 2/3 • Number of events 2 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.	20.0% 1/5 • Number of events 1 • Recorded from study screen through 30 days after the final study visit. Assessed systematically during study visits at time 0, 15, 30, 45, 60, 90 120, and 150 minutes after dosing and 1 day after all study visits by telephone call to subject.

Additional Information

Dr. Anne Cappola, PI

University of Pennsylvania

Phone: 215-573-5359

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place