Unacylated Ghrelin to Improve FuncTioning in PAD: The GIFT Trial

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03358355
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arm: 1
• Actual Duration (Months): 14.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The GIFT pilot study will investigate the optimal subcutaneous dose and safety of subcutaneously administered unacylated ghrelin in older people with peripheral artery disease (PAD).

Condition or Disease	Intervention/Treatment	Phase
Peripheral Artery Disease; PAD; Peripheral Arterial Disease	Drug: unacelyated ghrelin	Phase 1/Phase 2

Detailed Description

The pilot GIFT Trial will obtain preliminary evidence to identify the optimal dose of subcutaneously administered unacylated ghrelin in people with PAD. The results of this pilot study may be used to design a randomized trial of unacylated ghrelin, in subsequent study, to improve functioning and prevent mobility loss in older people with PAD.

In our primary specific aims, we will 1) establish the association of increasing doses of subcutaneous unacylated ghrelin with circulating levels of unacylated ghrelin 2) assess the safety of increasing doses of subcutaneously administered unacylated ghrelin in six patients with PAD age 55 and older. We will relate peak and Area Under the Curve values of unacylated ghrelin to brachial artery flow-mediated dilation (FMD) values. To achieve these aims, six PAD participants age 55 and older will receive a single subcutaneous injection of unacylated ghrelin at doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg, respectively, on three separate days at least one week apart. Unacylated ghrelin levels will be measured at baseline and at defined intervals after each subcutaneous injection (30 minutes, 60 minutes, 1.5 hours, 3 hours, 6 hours, 8 to 12 hours and 24 hours). Brachial artery FMD will be measured at baseline, before the unacylated ghrelin injection, approximately six hours, and 24 hours after each unacylated ghrelin injection. Blood will be collected and stored for potential later analyses of circulating biomarkers, such as inflammatory biomarkers.

This is a Phase I study to guide dose finding for a pilot study of unacylated ghrelin in people with PAD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Unacylated Ghrelin to Improve FuncTioning in PAD: The GIFT Trial
• Actual Study Start Date: Jun 7, 2016
• Actual Primary Completion Date: Aug 30, 2017
• Actual Study Completion Date: Aug 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Subcutaneous injection of unacylated ghrelin: Doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg	Drug: unacelyated ghrelin; We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.

Outcome Measures

Primary Outcome Measures

1. Levels of Unacylated Ghrelin [Baseline and at scheduled intervals up to 24 hours after baseline]

   Levels of unacylated ghrelin are measured before and after every injection

Secondary Outcome Measures

1. Brachial Artery Flow-mediated Dilation (FMD) [Baseline, 6-8 hours after baseline, 24 hours after baseline.]

   Brachial artery flow-mediated dilation in response to hyperemia. The outcome is reporting the MAX Relative FMD 60/90 (%), which is calculated as the highest FMD between the RH60 and RH90 results, as a percent.

Other Outcome Measures

1. Number of Participants Who Experienced Adverse Events [Within 24 hours after subcutaneous injection.]

   Adverse events

2. Number of Participants Who Experienced Serious Adverse Events [Within 24 hours after subcutaneous injection.]

   Serious adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. PAD patients age 55 and older

Exclusion Criteria:

1. Above or below-knee amputation, critical limb ischemia, and wheelchair confinement.

2. Cardiovascular event during the previous three months. [Note: Participants who have undergone coronary revascularization for a cardiac event during the previous three months may still qualify.]

3. Major medical illnesses including renal disease requiring dialysis, or cancer requiring treatment in the previous year.

4. Participation in another clinical trial or completion of a clinical trial in the previous month, unless they were in the control group of the previous trial.

5. Unwilling to attend nine study visits over approximately six months.

6. Surgery including lower extremity revascularization or orthopedic surgery in the previous month or anticipated surgery in the next three months.

7. Greater than 15 mmHg difference in blood pressure in both arm pressure measurements during the ankle brachial index (ABI), diagnosis of Raynaud's phenomenon, or unable to have the blood pressure checked in both arms.

8. Blood pressure < 90/50 at baseline.

9. Non-English speaking, a visual impairment that limits ability to read the consent, or a hearing impairment that interferes with study participation.

10. In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University

Investigators

• Principal Investigator: Mary McDermott, MD, Northwestern University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 4, 2017

More Information

Publications

None provided.

• Responsible Party: Mary McDermott, Jeremiah Stamler Professor, Northwestern University
• ClinicalTrials.gov Identifier: NCT03358355
• Other Study ID Numbers: STU00202400
• First Posted: Nov 30, 2017
• Last Update Posted: Mar 12, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mary McDermott, Jeremiah Stamler Professor, Northwestern University: PAD; unacylated ghrelin; Peripheral Artery Disease
• Additional relevant MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases

Study Results

Participant Flow

Arm/Group Title	Unacylated Ghrelin Intervention
Arm/Group Description	Subcutaneous injection of unacylated ghrelin: Doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.
Period Title: Overall Study
STARTED	9
COMPLETED	9
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Intervention
Arm/Group Description	Subcutaneous injection of unacylated ghrelin: Doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.
Overall Participants	9
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	9 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.0 (4.7)
Sex: Female, Male (Count of Participants)
Female	1 11.1%
Male	8 88.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	9 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 33.3%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	6 66.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	9 100%
Ankle-Brachial Index (ABI) (ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ratio]	0.69 (0.13)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.4 (4.6)
Six-minute walk distance (feet) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [feet]	1254.6 (531.8)

Outcome Measures

1. Primary Outcome

Title	Levels of Unacylated Ghrelin
Description	Levels of unacylated ghrelin are measured before and after every injection
Time Frame	Baseline and at scheduled intervals up to 24 hours after baseline

Outcome Measure Data

Analysis Population Description

Data originate from participants that received the injection and of which had data available

Arm/Group Title	Intervention(10 ug/kg)	Intervention(20 ug/kg)	Intervention(40 ug/kg)
Arm/Group Description	Subcutaneous injection of unacylated ghrelin: Doses of 10 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.	Subcutaneous injection of unacylated ghrelin: Doses of 20 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.	Subcutaneous injection of unacylated ghrelin: Doses of 40 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.
Measure Participants	5	6	4
unacylated ghrelin level - Pre	71.34 (58.67)	58.01 (29.98)	59.96 (31.34)
unacylated ghrelin level - 30 min	845.57 (300.12)	1522.36 (1339.83)	1102.99 (595.46)
unacylated ghrelin level - 60 min	772.33 (342.00)	1719.38 (2012.57)	1033.50 (623.85)
unacylated ghrelin level - 90 min	763.39 (446.80)	1998.58 (3043.75)	982.61 (584.37)
unacylated ghrelin level - 180 min	596.44 (371.88)	900.83 (1078.23)	694.51 (389.81)
unacylated ghrelin level - 360 min	373.09 (311.77)	492.23 (489.99)	410.49 (323.12)
unacylated ghrelin level - 720 min	240.94 (135.65)	304.62 (294.16)	339.46 (295.43)
unacylated ghrelin level - 1440 min	67.29 (48.64)	57.30 (27.34)	62.28 (34.03)

2. Secondary Outcome

Title	Brachial Artery Flow-mediated Dilation (FMD)
Description	Brachial artery flow-mediated dilation in response to hyperemia. The outcome is reporting the MAX Relative FMD 60/90 (%), which is calculated as the highest FMD between the RH60 and RH90 results, as a percent.
Time Frame	Baseline, 6-8 hours after baseline, 24 hours after baseline.

Outcome Measure Data

Analysis Population Description

Data originate from participants that received the injection and of which had data available

Arm/Group Title	Intervention(10 ug/kg)	Intervention(20 ug/kg)	Intervention(40 ug/kg)
Arm/Group Description	Subcutaneous injection of unacylated ghrelin: Doses of 10 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.	Subcutaneous injection of unacylated ghrelin: Doses of 20 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.	Subcutaneous injection of unacylated ghrelin: Doses of 40 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.
Measure Participants	5	5	6
Change in FMD 60/90 (%) from baseline to 6 hours	0.23	0.85	0.06
Change in FMD 60/90 (%) from baseline to 24-hours	1.14	-2.23	0.11

3. Other Pre-specified Outcome

Title	Number of Participants Who Experienced Adverse Events
Description	Adverse events
Time Frame	Within 24 hours after subcutaneous injection.

Outcome Measure Data

Analysis Population Description

Data originate from participants that received the injection and of which had data available

Arm/Group Title	Intervention(10 ug/kg)	Intervention(20 ug/kg)	Intervention(40 ug/kg)
Arm/Group Description	Subcutaneous injection of unacylated ghrelin: Doses of 10 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.	Subcutaneous injection of unacylated ghrelin: Doses of 20 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.	Subcutaneous injection of unacylated ghrelin: Doses of 40 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.
Measure Participants	5	6	6
New swelling	0 0%	0 NaN	0 NaN
New lightheadedness or dizziness	0 0%	1 NaN	0 NaN
New headaches	0 0%	1 NaN	0 NaN
New symptoms	0 0%	1 NaN	0 NaN

4. Other Pre-specified Outcome

Title	Number of Participants Who Experienced Serious Adverse Events
Description	Serious adverse events
Time Frame	Within 24 hours after subcutaneous injection.

Outcome Measure Data

Analysis Population Description

Data originate from participants that received the injection and of which had data available

Arm/Group Title	Intervention
Arm/Group Description	Subcutaneous injection of unacylated ghrelin: Doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.
Measure Participants	9
Count of Participants [Participants]	1 11.1%

Adverse Events

Time Frame	Adverse events will be monitored continuously throughout the study and will be reported to the DSMB and IRB in a timely manner according to pre-specified requirements. We will minimize risk by observing study participants for approximately 8-12 hours after each of the three doses of unacylated ghrelin.
Adverse Event Reporting Description	Participant that received any injection were monitored for adverse events.
Arm/Group Title	Intervention(10 ug/kg)		Intervention(20 ug/kg)		Intervention(40 ug/kg)
Arm/Group Description	Subcutaneous injection of unacylated ghrelin: Doses of 10 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.		Subcutaneous injection of unacylated ghrelin: Doses of 20 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.		Subcutaneous injection of unacylated ghrelin: Doses of 40 ug/kg unacelyated ghrelin: We will test doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg of unacylated ghrelin on three separate days for each participant.
All Cause Mortality
	Intervention(10 ug/kg)		Intervention(20 ug/kg)		Intervention(40 ug/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Intervention(10 ug/kg)		Intervention(20 ug/kg)		Intervention(40 ug/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Cardiac disorders
Cardiovascular event	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Other (Not Including Serious) Adverse Events
	Intervention(10 ug/kg)		Intervention(20 ug/kg)		Intervention(40 ug/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		1/6 (16.7%)		0/6 (0%)
General disorders
New swelling	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
New lightheadedness or dizziness	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
New headaches	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
New symptoms	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (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.