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CompletedNCT00395291Updated Feb 20, 2017Results posted

Growth Hormone Secretagogue MK-0677 Effect on IGF-1 Levels in ESRD Patients

An interventional study of MK-0677 and Placebo in Chronic Kidney Disease and End Stage Renal Disease, sponsored by University of Virginia. Completed at 1 site in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2017-02-20.

Sponsored by University of Virginia · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
49
Allocation
Randomized
Ages
18 Years to 99 Years
Sex
All
01

Study summary

The objective of this study is to determine MK-0677 increases IGF-1 in patients with end stage renal disease (ESRD) on hemodialysis.

Read the detailed description

With development and progression of chronic kidney disease (CKD) to end stage renal disease (ESRD), malnutrition becomes an increasingly severe problem. This is thought to occur from two mechanisms: decreased appetite secondary to uremia and development of a catabolic inflammatory milieu. Patients experience decreased muscle mass and functional activity associated with increased morbidity and mortality. Many therapies to improve poor nutritional state have been used with little success. Growth hormone (GH) and insulin like growth hormone (IGF-1) improve muscle mass, quality of life, nutritional parameters, immune and physical functions but must be given parenterally and are limited by expense and patient compliance. Recently, the endogenous GH receptor secretagogue (GHRS) ghrelin has been shown to raise endogenous GH and improve food intake but must be given parenterally and is not available. The experimental drug MK-0677, a synthetic GHRS, ghrelin mimetic, which is given orally, has recently been shown to increase IGF-1 and muscle mass in the elderly. Its effects in CKD and ESRD are unknown. We will study the effects of MK-0677 on renal patients. Specifically, we hope to show that the drug increases IGF-1 in renal patients, and has similar effects to exogenous GH and IGF-1. Subjects will be ESRD hemodialysis patients. This protocol is an investigator-initiated, randomized, double-blind crossover, placebo-controlled pilot study. The study's primary outcome is IGF-1 levels for subjects. Secondary outcomes will be levels of cytokines, esterase, leptin, insulin, ghrelin, TNF-alpha, CRPs, IL-1, IL-6, IL-10, and adiponectin.

02

Conditions studied

  • Chronic Kidney Disease
  • End Stage Renal Disease

Keywords

  • Chronic kidney disease
  • End stage renal disease
03

In context

Kidney Diseases

3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.

This study's enrollment of 49 is below the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.

Browse Kidney Diseases studies →

Lead sponsor

University of Virginia is the lead sponsor of 653 studies on the registry; 134 are open to participants now.

Of its 60 completed or terminated interventional studies of FDA-regulated products, 41 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 99 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • GFR by the MDRD estimate \< 30ml/minute/1.73m2 or on hemodialysis

Exclusion criteria

Exclusion Criteria:

  • Body mass index greater than 35 kg/m2, or morbid obesity
  • Uncontrolled hypothyroidism, defined as an elevated serum thyroid stimulating hormone (THS) and a free serum thyroxine (T4) less than the lower limit of normal, when tested at baseline (Patients requiring thyroid replacement during the study may continue.)
  • Uncontrolled hyperthyroidism, defined as a TSH less than the lower limit of normal and an elevated free T4, when tested at baseline
  • Hemoglobin \<10 Gm/dl
  • Elevated serum transaminases (>2.0 times the upper limit of normal at baseline)

  • Diabetes with one of more of the following:

    1. Poorly controlled diabetes as defined by a HbA1C > 7.0% at baseline)
    2. Proliferative diabetic retinopathy [To participate in this study, diabetic patients will need to have had a dilated ophthalmology exam within 12 months of enrollment. Individuals who already have extensive background retinopathy will need to have a dilated ophthalmology exam within the 3 months of enrollment. Patients with pre-proliferative or proliferative retinopathy will be excluded].
    3. Unwilling or unable to check blood glucose at home at least daily.
  • Currently receiving a systemic corticosteroid dose of >10 mg prednisone (or equivalent), or patient has received, for a duration > 30 days in the previous 6 months (i.e., prior to signing the informed consent form), a systemic corticosteroid dose of > 10 mg prednisone (or equivalent). (The previous use, or current use, of a topical or inhaled corticosteroid is allowed.)
  • Currently taking or previously on an anabolic steroid or growth hormone at any dose, or for any duration, during the 12 months prior to study entry.
  • Significant end-organ disease, other than kidney disease, which, in the opinion of the investigator may pose an added risk to the patient, confound the study results, or impair the patient's ability to complete the trial.

  • Any of the following disorders within 6 months prior to baseline:

    1. Acute coronary syndrome (e.g., myocardial infarction or unstable angina)
    2. Coronary artery intervention (e.g., coronary bypass graft [CABG], percutaneous transluminal coronary angioplasty [PTCA]).
    3. Stroke or transient ischemic neurological disorder (e.g. transient ischemic attack [TIA])
  • New or worsening signs or symptoms of coronary heart disease within the 3 months prior to baseline.
  • NYHA (New York Heart Association)Class III or IV congestive heart failure (definitions shown in Appendix A)
  • Uncontrolled hypertension when checked at screening visit: as evidenced by > 160 systolic and/or 100 diastolic (measured in dominant or non-dialysis access arm, after at least 5 minutes, sitting)
  • Cancer, or diagnosis of malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or adequately treated in situ cervical cancer.
  • Active carpal tunnel syndrome
  • Patient is, in the opinion of the investigator, mentally or legally incapacitated such that informed consent cannot be obtained or such that adherence to the study procedures and dosing regimens is questionable.
  • Patient is, at study entry, a regular user (including "recreational use") of illicit drugs or had a recent history (within the last 5 years) of drug or alcohol abuse.
  • Patient plans to relocate or change to a different dialysis center during the study, rendering follow-up per protocol, impractical.
  • Patient is participating in, or has participated in, another study with an investigational drug within 30 days prior to signing the informed consent form.
  • Women who are pregnant or lactating
  • HIV positive (medical history review and patient report)
  • Patient is on potent CYP3A4 Inhibitor or Inducer Drugs within one week of starting study drug.
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
49 participants (actual)

Study arms

  • Experimental
    MK-0677 then Placebo

    MK-0677 and Placebo - All subjects were given MK-0677 for a 30 +/- 7 days and then they were given a placebo for 30 +/- 7 days.

    Drug: MK-0677 · Drug: Placebo

  • Experimental
    Placebo then MK-0677

    MK-0677 and Placebo - All subjects were given Placebo for a 30 +/- 7 days and then they were given MK-0677 for 30 +/- 7 days.

    Drug: MK-0677 · Drug: Placebo

Interventions

  • DrugMK-0677

    The dosage of the drug is 25mg, subjects will take one pill a day for about 30 days.

  • DrugPlacebo

    Placebo

06

What researchers measure

Primary outcomes

  1. Change in IGF-1 After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the IGF-1 levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention

Secondary outcomes

  1. Change in Acyl-Ghrelin After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the Acyl-Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention.

  2. Change in Leptin After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the Leptin levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention

  3. Change in Insulin After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the Insulin levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention

  4. Change in Des-Acyl Ghrelin After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the Des-Acyl Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention

  5. Change in TNF-alpha After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the TNF-alpha levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention

  6. Change in CRPs After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the CRPs levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention

  7. Change in IL-1 After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the IL-1 levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention

  8. Changes in the Following Level: IL-6

    Change in IL-6 after 30 days of intervention.

    Time frame: After the subject has comleted their last visit

  9. Change in IL-10 After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the IL-10 levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention

  10. Change in Esterase After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the Esterase levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention

  11. Change in Adiponectin After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the Adiponectin levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention

  12. Change in Ghrelin After 30 Days of Intervention Compared to Baseline Level.

    Looking for a change in the Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.

    Time frame: Baseline and after 30 days of intervention

07

Results

Posted Jan 6, 2012
Limitations and caveats
We completed the appropriate number of subjects to get the statistical data needed. We had several screen fails (subjects that did not meet the inclusion/exclusion criteria.)

Participant flow

We recruited our subjects from 3 clinics at the University of Virginia. Our clinics were located at the Dialysis Units in Charlottesville, VA, Fisherville, VA, and Zion Crossroads, VA. Subjects were recruited into this study between March 2007 and August 2008.

First Intervention
Participant flow — First Intervention
MilestoneMK-0677 First, Then PlaceboPlacebo First, Then MK-0677
Started179
Completed159
Not completed20
Washout Period for 30 Days
Participant flow — Washout Period for 30 Days
MilestoneMK-0677 First, Then PlaceboPlacebo First, Then MK-0677
Started159
Completed139
Not completed20
Second Intervention
Participant flow — Second Intervention
MilestoneMK-0677 First, Then PlaceboPlacebo First, Then MK-0677
Started139
Completed139
Not completed00

Outcome measures

PrimaryChange in IGF-1 After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the IGF-1 levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention
Reported as:
Mean · ng/ml
Change in IGF-1 After 30 Days of Intervention Compared to Baseline Level.
ng/mlMK-0677Placebo
Change in IGF-1 After 30 Days of Intervention Compared to Baseline Level.92.7 ± 62.36.7 ± 40.2
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = <0.001 (The IGF-1 data were analyzed on the natural logarithmic scale via a linear mixed model in correspondence to a 2-period crossover design ANCOVA.)
SecondaryChange in Acyl-Ghrelin After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the Acyl-Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention.
Reported as:
Mean · pg/ml
Change in Acyl-Ghrelin After 30 Days of Intervention Compared to Baseline Level.
pg/mlMK-0677Placebo
Change in Acyl-Ghrelin After 30 Days of Intervention Compared to Baseline Level.-23.4 ± 68.93.5 ± 150.3
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = 0.169The Acyl-Ghrelin data were analyzed on the natural logarithmic scale via a linear mixed model in correspondence to a 2-period crossover design ANCOVA.
SecondaryChange in Leptin After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the Leptin levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention
Reported as:
Mean · ng/ml
Change in Leptin After 30 Days of Intervention Compared to Baseline Level.
ng/mlMK-0677Placebo
Change in Leptin After 30 Days of Intervention Compared to Baseline Level.24.4 ± 50.2-6.9 ± 30.4
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = 0.063The Leptin data were analyzed on the natural logarithmic scale via a linear mixed model in correspondence to a 2-period crossover design ANCOVA.
SecondaryChange in Insulin After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the Insulin levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention
Reported as:
Mean · uIU/ml
Change in Insulin After 30 Days of Intervention Compared to Baseline Level.
uIU/mlMK-0677Placebo
Change in Insulin After 30 Days of Intervention Compared to Baseline Level.3.77 ± 10.5-.2 ± 12.5
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = 0.075The insulin data were analyzed on the natural logarithmic scale via a linear mixed model in correspondence to a 2-period crossover design ANCOVA.
SecondaryChange in Des-Acyl Ghrelin After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the Des-Acyl Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention
Reported as:
Mean · pg/ml
Change in Des-Acyl Ghrelin After 30 Days of Intervention Compared to Baseline Level.
pg/mlMK-0677Placebo
Change in Des-Acyl Ghrelin After 30 Days of Intervention Compared to Baseline Level.30.2 ± 201.5-44.05 ± 157.4
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = .782
SecondaryChange in TNF-alpha After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the TNF-alpha levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention
Reported as:
Mean · pg/ml
Change in TNF-alpha After 30 Days of Intervention Compared to Baseline Level.
pg/mlMK-0677Placebo
Change in TNF-alpha After 30 Days of Intervention Compared to Baseline Level.1.2 ± 5.9-0.7 ± 14.6
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = 0.385The TNF-a data were analyzed on the natural logarithmic scale via a linear mixed model in correspondence to a 2-period crossover design ANCOVA.
SecondaryChange in CRPs After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the CRPs levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention
Reported as:
Mean · mg/ml
Change in CRPs After 30 Days of Intervention Compared to Baseline Level.
mg/mlMK-0677Placebo
Change in CRPs After 30 Days of Intervention Compared to Baseline Level.2.6 ± 13.46.0 ± 32.7
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = 0.929The CRPs data were analyzed on the natural logarithmic scale via a linear mixed model in correspondence to a 2-period crossover design ANCOVA.
SecondaryChange in IL-1 After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the IL-1 levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention
Reported as:
Mean · pg/ml
Change in IL-1 After 30 Days of Intervention Compared to Baseline Level.
pg/mlMK-0677Placebo
Change in IL-1 After 30 Days of Intervention Compared to Baseline Level.0.0 ± 0.2-0.0 ± 0.3
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = 0.905The IL-1 data were analyzed on the natural logarithmic scale via a linear mixed model in correspondence to a 2-period crossover design ANCOVA.
SecondaryChanges in the Following Level: IL-6

Change in IL-6 after 30 days of intervention.

Time frame:
After the subject has comleted their last visit
Reported as:
Mean · pg/mL
Changes in the Following Level: IL-6
pg/mLMK-0677Placebo
Changes in the Following Level: IL-63.1 ± 5.20.8 ± 6.9
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = 0.233
SecondaryChange in IL-10 After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the IL-10 levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention
Reported as:
Mean · pg/ml
Change in IL-10 After 30 Days of Intervention Compared to Baseline Level.
pg/mlMK-0677Placebo
Change in IL-10 After 30 Days of Intervention Compared to Baseline Level.-0.1 ± 1.90.7 ± 1.7
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = 0.277The IL-10 data were analyzed on the natural logarithmic scale via a linear mixed model in correspondence to a 2-period crossover design ANCOVA.
SecondaryChange in Esterase After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the Esterase levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention
Reported as:
Mean · units/ml
Change in Esterase After 30 Days of Intervention Compared to Baseline Level.
units/mlMK-0677Placebo
Change in Esterase After 30 Days of Intervention Compared to Baseline Level.-1.6 ± 10.3-1.3 ± 12.6
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = 0.875The esterase data were analyzed on the natural logarithmic scale via a linear mixed model in correspondence to a 2-period crossover design ANCOVA.
SecondaryChange in Adiponectin After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the Adiponectin levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention
Reported as:
Mean · ng/ml
Change in Adiponectin After 30 Days of Intervention Compared to Baseline Level.
ng/mlMK-0677Placebo
Change in Adiponectin After 30 Days of Intervention Compared to Baseline Level.1242.0 ± 7858.1735.1 ± 4485.0
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = 0.545The adiponectin data were analyzed on the natural logarithmic scale via a linear mixed model in correspondence to a 2-period crossover design ANCOVA.
SecondaryChange in Ghrelin After 30 Days of Intervention Compared to Baseline Level.

Looking for a change in the Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.

Time frame:
Baseline and after 30 days of intervention
Reported as:
Mean · pg/ml
Change in Ghrelin After 30 Days of Intervention Compared to Baseline Level.
pg/mlMK-0677Placebo
Change in Ghrelin After 30 Days of Intervention Compared to Baseline Level.6.9 ± 162.5-40.5 ± 192.5
Statistical analysis
  • MK-0677 vs Placebo · ANCOVA · p = 0.900Total ghrelin data were analyzed on the natural logarithmic scale via a linear mixed model in correspondence to a 2-period crossover design ANCOVA.

Adverse events

Collected over Adverse Events were collect from the time the subject started the first intervention and ended two weeks from the last study visit.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
MK-0677—4/26 (15.4%)5/26 (19.2%)
Placebo—3/26 (11.5%)0/26 (0%)
Most frequent serious events
Most frequent serious events
EventMK-0677Placebo
Renal FailureRenal and urinary disorders1/260/26
CardiomyopathyCardiac disorders0/261/26
Ischemic ColitisGastrointestinal disorders1/260/26
Eroded Arteriovenous Dialysis GraftSurgical and medical procedures1/260/26
Perm-A-Cath Line InfectionInfections and infestations1/260/26
Congestive Heart FailureCardiac disorders1/260/26
HyperkalemiaCardiac disorders0/261/26
Supratherapeutic INRBlood and lymphatic system disorders0/261/26
Most frequent other events
Most frequent other events
EventMK-0677Placebo
Cold, Cough, Sinus CongestionRespiratory, thoracic and mediastinal disorders3/260/26
Nausea, Upset StomachGastrointestinal disorders2/260/26

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Entire Study Population
<=18 years0
Between 18 and 65 years18
>=65 years8
Age, Continuous
Age, Continuous(years)Entire Study Population
Mean57.3 ± 14.4
Gender
Gender(Participants)Entire Study Population
Female8
Male18
Region of Enrollment
Region of Enrollment(participants)Entire Study Population
United States26
08

Study locations

1 site
  • University of Virginia
    Charlottesville, Virginia 22908, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 20, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00395291
Lead sponsor
University of Virginia
Collaborators
National Institutes of Health (NIH), Merck Sharp & Dohme LLC
Responsible party
Warren K Bolton (Principal Investigator, University of Virginia) — Principal investigator
First posted
Nov 2, 2006
Start date
Aug 2006
Primary completion
Jan 2009
Completion
May 2010
Results posted
Jan 6, 2012
Last update
Feb 20, 2017

Study contacts

Warren K Bolton, MD
principal investigator · University of Virginia

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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