PAD, Peripheral Arterial Disease, Peripheral Artery Disease
Conditions
Keywords
PAD, unacylated ghrelin, Peripheral Artery Disease
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).
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.
Interventions
DRUGunacelyated 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.
Sponsors
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Adverse Events | Within 24 hours after subcutaneous injection. | Adverse events |
| Number of Participants Who Experienced Serious Adverse Events | Within 24 hours after subcutaneous injection. | Serious adverse events |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention 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. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 71.0 years STANDARD_DEVIATION 4.7 |
| Ankle-Brachial Index (ABI) | 0.69 ratio STANDARD_DEVIATION 0.13 |
| Body Mass Index (BMI) | 30.4 kg/m^2 STANDARD_DEVIATION 4.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 8 Participants |
| Six-minute walk distance | 1254.6 feet STANDARD_DEVIATION 531.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 1 / 6 | 0 / 6 |
| serious Total, serious adverse events | 1 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Levels of Unacylated Ghrelin
Levels of unacylated ghrelin are measured before and after every injection
Time frame: Baseline and at scheduled intervals up to 24 hours after baseline
Population: Data originate from participants that received the injection and of which had data available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention(10 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - Pre | 71.34 pg/ml | Standard Deviation 58.67 |
| Intervention(10 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 30 min | 845.57 pg/ml | Standard Deviation 300.12 |
| Intervention(10 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 60 min | 772.33 pg/ml | Standard Deviation 342 |
| Intervention(10 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 90 min | 763.39 pg/ml | Standard Deviation 446.8 |
| Intervention(10 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 180 min | 596.44 pg/ml | Standard Deviation 371.88 |
| Intervention(10 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 360 min | 373.09 pg/ml | Standard Deviation 311.77 |
| Intervention(10 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 720 min | 240.94 pg/ml | Standard Deviation 135.65 |
| Intervention(10 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 1440 min | 67.29 pg/ml | Standard Deviation 48.64 |
| Intervention(20 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 60 min | 1719.38 pg/ml | Standard Deviation 2012.57 |
| Intervention(20 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 720 min | 304.62 pg/ml | Standard Deviation 294.16 |
| Intervention(20 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 90 min | 1998.58 pg/ml | Standard Deviation 3043.75 |
| Intervention(20 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 180 min | 900.83 pg/ml | Standard Deviation 1078.23 |
| Intervention(20 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 360 min | 492.23 pg/ml | Standard Deviation 489.99 |
| Intervention(20 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - Pre | 58.01 pg/ml | Standard Deviation 29.98 |
| Intervention(20 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 30 min | 1522.36 pg/ml | Standard Deviation 1339.83 |
| Intervention(20 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 1440 min | 57.30 pg/ml | Standard Deviation 27.34 |
| Intervention(40 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 60 min | 1033.50 pg/ml | Standard Deviation 623.85 |
| Intervention(40 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 30 min | 1102.99 pg/ml | Standard Deviation 595.46 |
| Intervention(40 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - Pre | 59.96 pg/ml | Standard Deviation 31.34 |
| Intervention(40 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 90 min | 982.61 pg/ml | Standard Deviation 584.37 |
| Intervention(40 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 720 min | 339.46 pg/ml | Standard Deviation 295.43 |
| Intervention(40 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 360 min | 410.49 pg/ml | Standard Deviation 323.12 |
| Intervention(40 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 180 min | 694.51 pg/ml | Standard Deviation 389.81 |
| Intervention(40 ug/kg) | Levels of Unacylated Ghrelin | unacylated ghrelin level - 1440 min | 62.28 pg/ml | Standard Deviation 34.03 |
Secondary
Brachial Artery Flow-mediated Dilation (FMD)
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.
Population: Data originate from participants that received the injection and of which had data available
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intervention(10 ug/kg) | Brachial Artery Flow-mediated Dilation (FMD) | Change in FMD 60/90 (%) from baseline to 6 hours | 0.23 ratio |
| Intervention(10 ug/kg) | Brachial Artery Flow-mediated Dilation (FMD) | Change in FMD 60/90 (%) from baseline to 24-hours | 1.14 ratio |
| Intervention(20 ug/kg) | Brachial Artery Flow-mediated Dilation (FMD) | Change in FMD 60/90 (%) from baseline to 6 hours | 0.85 ratio |
| Intervention(20 ug/kg) | Brachial Artery Flow-mediated Dilation (FMD) | Change in FMD 60/90 (%) from baseline to 24-hours | -2.23 ratio |
| Intervention(40 ug/kg) | Brachial Artery Flow-mediated Dilation (FMD) | Change in FMD 60/90 (%) from baseline to 6 hours | 0.06 ratio |
| Intervention(40 ug/kg) | Brachial Artery Flow-mediated Dilation (FMD) | Change in FMD 60/90 (%) from baseline to 24-hours | 0.11 ratio |
Other Pre-specified
Number of Participants Who Experienced Adverse Events
Adverse events
Time frame: Within 24 hours after subcutaneous injection.
Population: Data originate from participants that received the injection and of which had data available
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intervention(10 ug/kg) | Number of Participants Who Experienced Adverse Events | New swelling | 0 Participants |
| Intervention(10 ug/kg) | Number of Participants Who Experienced Adverse Events | New lightheadedness or dizziness | 0 Participants |
| Intervention(10 ug/kg) | Number of Participants Who Experienced Adverse Events | New headaches | 0 Participants |
| Intervention(10 ug/kg) | Number of Participants Who Experienced Adverse Events | New symptoms | 0 Participants |
| Intervention(20 ug/kg) | Number of Participants Who Experienced Adverse Events | New symptoms | 1 Participants |
| Intervention(20 ug/kg) | Number of Participants Who Experienced Adverse Events | New swelling | 0 Participants |
| Intervention(20 ug/kg) | Number of Participants Who Experienced Adverse Events | New headaches | 1 Participants |
| Intervention(20 ug/kg) | Number of Participants Who Experienced Adverse Events | New lightheadedness or dizziness | 1 Participants |
| Intervention(40 ug/kg) | Number of Participants Who Experienced Adverse Events | New symptoms | 0 Participants |
| Intervention(40 ug/kg) | Number of Participants Who Experienced Adverse Events | New lightheadedness or dizziness | 0 Participants |
| Intervention(40 ug/kg) | Number of Participants Who Experienced Adverse Events | New headaches | 0 Participants |
| Intervention(40 ug/kg) | Number of Participants Who Experienced Adverse Events | New swelling | 0 Participants |
Other Pre-specified
Number of Participants Who Experienced Serious Adverse Events
Serious adverse events
Time frame: Within 24 hours after subcutaneous injection.
Population: Data originate from participants that received the injection and of which had data available
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention(10 ug/kg) | Number of Participants Who Experienced Serious Adverse Events | 1 Participants |