CClinicalTrials.gg
CompletedNCT03358355GIFTUpdated Mar 12, 2020Results posted

Unacylated Ghrelin to Improve FuncTioning in PAD: The GIFT Trial

A Phase 1/2 interventional study of unacelyated ghrelin in Peripheral Artery Disease, PAD and Peripheral Arterial Disease, sponsored by Northwestern University. Completed at 1 site in United States. Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2020-03-12.

Sponsored by Northwestern University · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
9
Allocation
Not applicable
Ages
55 Years and older
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Peripheral Artery Disease
  • PAD
  • Peripheral Arterial Disease

Keywords

  • PAD
  • unacylated ghrelin
  • Peripheral Artery Disease
03

Who can participate

Ages eligible
55 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. PAD patients age 55 and older

Exclusion criteria

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.
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
9 participants (actual)

Study arms

  • Experimental
    Intervention

    Subcutaneous injection of unacylated ghrelin: Doses of 10 ug/kg, 20 ug/kg, and 40 ug/kg

    Drug: unacelyated ghrelin

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.

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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.

Other outcomes

  1. Number of Participants Who Experienced Adverse Events

    Adverse events

    Time frame: Within 24 hours after subcutaneous injection.

  2. Number of Participants Who Experienced Serious Adverse Events

    Serious adverse events

    Time frame: Within 24 hours after subcutaneous injection.

06

Results

Posted Mar 12, 2020

Participant flow

Participant flow — Overall Study
MilestoneUnacylated Ghrelin Intervention
Started9
Completed9
Not completed0

Outcome measures

PrimaryLevels 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
Reported as:
Mean · pg/ml
Levels of Unacylated Ghrelin
pg/mlIntervention(10 ug/kg)Intervention(20 ug/kg)Intervention(40 ug/kg)
unacylated ghrelin level - Pre71.34 ± 58.6758.01 ± 29.9859.96 ± 31.34
unacylated ghrelin level - 30 min845.57 ± 300.121522.36 ± 1339.831102.99 ± 595.46
unacylated ghrelin level - 60 min772.33 ± 342.001719.38 ± 2012.571033.50 ± 623.85
unacylated ghrelin level - 90 min763.39 ± 446.801998.58 ± 3043.75982.61 ± 584.37
unacylated ghrelin level - 180 min596.44 ± 371.88900.83 ± 1078.23694.51 ± 389.81
unacylated ghrelin level - 360 min373.09 ± 311.77492.23 ± 489.99410.49 ± 323.12
unacylated ghrelin level - 720 min240.94 ± 135.65304.62 ± 294.16339.46 ± 295.43
unacylated ghrelin level - 1440 min67.29 ± 48.6457.30 ± 27.3462.28 ± 34.03
SecondaryBrachial 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.
Reported as:
Median · ratio
Brachial Artery Flow-mediated Dilation (FMD)
ratioIntervention(10 ug/kg)Intervention(20 ug/kg)Intervention(40 ug/kg)
Change in FMD 60/90 (%) from baseline to 6 hours0.23 (-0.47 to 2.21)0.85 (0.63 to 1.17)0.06 (-1.56 to 1.67)
Change in FMD 60/90 (%) from baseline to 24-hours1.14 (0.99 to 1.94)-2.23 (-2.70 to -2.07)0.11 (-0.83 to 0.55)
Other pre-specifiedNumber of Participants Who Experienced Adverse Events

Adverse events

Time frame:
Within 24 hours after subcutaneous injection.
Reported as:
Count of participants · Participants
Number of Participants Who Experienced Adverse Events
ParticipantsIntervention(10 ug/kg)Intervention(20 ug/kg)Intervention(40 ug/kg)
New swelling000
New lightheadedness or dizziness010
New headaches010
New symptoms010
Other pre-specifiedNumber of Participants Who Experienced Serious Adverse Events

Serious adverse events

Time frame:
Within 24 hours after subcutaneous injection.
Reported as:
Count of participants · Participants
Number of Participants Who Experienced Serious Adverse Events
ParticipantsIntervention
Number of Participants Who Experienced Serious Adverse Events1

Adverse events

Collected over 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.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Intervention(10 ug/kg)0/6 (0%)1/6 (16.7%)0/6 (0%)
Intervention(20 ug/kg)0/6 (0%)0/6 (0%)1/6 (16.7%)
Intervention(40 ug/kg)0/6 (0%)0/6 (0%)0/6 (0%)
Most frequent serious events
Most frequent serious events
EventIntervention(10 ug/kg)Intervention(20 ug/kg)Intervention(40 ug/kg)
Cardiovascular eventCardiac disorders1/60/60/6
Most frequent other events
Most frequent other events
EventIntervention(10 ug/kg)Intervention(20 ug/kg)Intervention(40 ug/kg)
New lightheadedness or dizzinessGeneral disorders0/61/60/6
New headachesGeneral disorders0/61/60/6
New symptomsGeneral disorders0/61/60/6
New swellingGeneral disorders0/60/60/6

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Intervention
<=18 years0
Between 18 and 65 years0
>=65 years9
Age, Continuous
Age, Continuous(years)Intervention
Mean71.0 ± 4.7
Sex: Female, Male
Sex: Female, Male(Participants)Intervention
Female1
Male8
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Intervention
Hispanic or Latino0
Not Hispanic or Latino9
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Intervention
American Indian or Alaska Native3
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White6
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Intervention
United States9
Ankle-Brachial Index (ABI)
Ankle-Brachial Index (ABI)(ratio)Intervention
Mean0.69 ± 0.13
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)Intervention
Mean30.4 ± 4.6

1 further baseline measures are reported on the registry.

07

Study locations

1 site
  • Northwestern University Feinberg School of Medicine
    Chicago, Illinois 60611, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Apr 4, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03358355
Lead sponsor
Northwestern University
Responsible party
Mary McDermott (Jeremiah Stamler Professor, Northwestern University) — Principal investigator
First posted
Nov 30, 2017
Start date
Jun 7, 2016
Primary completion
Aug 30, 2017
Completion
Aug 30, 2017
Results posted
Mar 12, 2020
Last update
Mar 12, 2020

Study contacts

Mary McDermott, MD
principal investigator · Northwestern University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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