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Growth Hormone Secretagogue MK-677 Therapy Effect on IGF-1 Levels in CKD and ESRD Patients
This study is currently recruiting participants.
Verified by University of Virginia, September 2006
Sponsors and Collaborators: University of Virginia
National Institutes of Health (NIH)
Merck and Company
Information provided by: University of Virginia
ClinicalTrials.gov Identifier: NCT00395291
  Purpose

The objective of this study is to determine MK-677 increases IGF-1 in patients with stage 4/5 chronic kidney disease (CKD)and/or in patients with end stage renal disease (ESRD) on hemodialysis.


Condition Intervention
Chronic Kidney Disease
End Stage Renal Disease
Drug: MK-677

Drug Information available for: Insulin-like growth factor I Mecasermin rinfabate Somatotropin Somatropin Ibutamoren mesylate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Pharmacodynamics Study
Official Title: Growth Hormone Secretagogue MK-677 Therapy Effect on IGF-1 Levels in CKD and ESRD Patients

Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Change in IGF-1 after 30 days of intervention

Secondary Outcome Measures:
  • Change in the following levels
  • cytokines
  • leptin
  • insulin
  • ghrelin
  • TNF-alpha
  • CRPs
  • IL-1
  • IL-6
  • IL-10

Estimated Enrollment: 52
Study Start Date: August 2006
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-677, 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-677 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 have CKD stage 4/5 or 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, leptin, insulin, ghrelin, TNF-alpha, CRPs, IL-1, IL-6 and IL-10.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00395291

Contacts
Contact: Lori Ratliff, RN 434-924-1572 lbr@virginia.edu
Contact: Warren K Bolton, MD 434-982-3577 wkb5s@virginia.edu

Locations
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Principal Investigator: Warren K Bolton, MD            
Sponsors and Collaborators
University of Virginia
Merck and Company
Investigators
Principal Investigator: Warren K Bolton, MD University of Virginia
  More Information

Study ID Numbers: 12569
Study First Received: November 1, 2006
Last Updated: November 1, 2006
ClinicalTrials.gov Identifier: NCT00395291  
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Virginia:
Chronic kidney disease
End stage renal disease

Study placed in the following topic categories:
Renal Insufficiency
Urologic Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Kidney Diseases
Kidney Failure

ClinicalTrials.gov processed this record on January 16, 2009