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

Purpose

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

Condition	Intervention
Chronic Kidney Disease End Stage Renal Disease	Drug: MK-0677 Drug: Placebo


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Growth Hormone Secretagogue MK-0677 Effect on IGF-1 Levels in ESRD Patients

Resource links provided by NLM:

MedlinePlus related topics: Chronic Kidney Disease Diabetes Medicines Hormones Kidney Diseases Kidney Failure

U.S. FDA Resources

Further study details as provided by University of Virginia:

Primary Outcome Measures:

Change in IGF-1 After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention ] [ Designated as safety issue: No ]
Looking for a change in the IGF-1 levels after the subject has been on intervention for 30 days compared to baseline levels.

Secondary Outcome Measures:

Change in Acyl-Ghrelin After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention. ] [ Designated as safety issue: No ]
Looking for a change in the Acyl-Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.
Change in Leptin After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention ] [ Designated as safety issue: No ]
Looking for a change in the Leptin levels after the subject has been on intervention for 30 days compared to baseline levels.
Change in Insulin After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention ] [ Designated as safety issue: No ]
Looking for a change in the Insulin levels after the subject has been on intervention for 30 days compared to baseline levels.
Change in Des-Acyl Ghrelin After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention ] [ Designated as safety issue: No ]
Looking for a change in the Des-Acyl Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.
Change in TNF-alpha After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention ] [ Designated as safety issue: No ]
Looking for a change in the TNF-alpha levels after the subject has been on intervention for 30 days compared to baseline levels.
Change in CRPs After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention ] [ Designated as safety issue: No ]
Looking for a change in the CRPs levels after the subject has been on intervention for 30 days compared to baseline levels.
Change in IL-1 After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention ] [ Designated as safety issue: No ]
Looking for a change in the IL-1 levels after the subject has been on intervention for 30 days compared to baseline levels.
Changes in the Following Level: IL-6 [ Time Frame: After the subject has comleted their last visit ] [ Designated as safety issue: No ]
Change in IL-6 after 30 days of intervention.
Change in IL-10 After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention ] [ Designated as safety issue: No ]
Looking for a change in the IL-10 levels after the subject has been on intervention for 30 days compared to baseline levels.
Change in Esterase After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention ] [ Designated as safety issue: No ]
Looking for a change in the Esterase levels after the subject has been on intervention for 30 days compared to baseline levels.
Change in Adiponectin After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention ] [ Designated as safety issue: No ]
Looking for a change in the Adiponectin levels after the subject has been on intervention for 30 days compared to baseline levels.
Change in Ghrelin After 30 Days of Intervention Compared to Baseline Level. [ Time Frame: Baseline and after 30 days of intervention ] [ Designated as safety issue: No ]
Looking for a change in the Ghrelin levels after the subject has been on intervention for 30 days compared to baseline levels.


Enrollment:	49
Study Start Date:	August 2006
Study Completion Date:	May 2010
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: MK-0677, 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 The dosage of the drug is 25mg, subjects will take one pill a day for about 30 days. Drug: Placebo Placebo

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.

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations


United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908

Sponsors and Collaborators

University of Virginia

National Institutes of Health (NIH)

Merck Sharp & Dohme Corp.

Investigators


Principal Investigator:	Warren K Bolton, MD	University of Virginia

More Information

No publications provided


Responsible Party:	Warren K Bolton, Principal Investigator, University of Virginia
ClinicalTrials.gov Identifier:	NCT00395291 History of Changes
Other Study ID Numbers:	12569
Study First Received:	November 1, 2006
Results First Received:	August 2, 2011
Last Updated:	January 14, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Virginia:


Chronic kidney disease End stage renal disease

Additional relevant MeSH terms:


Kidney Diseases Kidney Failure, Chronic Renal Insufficiency, Chronic Renal Insufficiency Urologic Diseases

ClinicalTrials.gov processed this record on March 01, 2015