Growth Hormone Secretagogue MK-0677's Effect on Lean Body Mass in Chronic Kidney Disease Stage 4/5 Subjects

NCT01343641 | Withdrawn Phase 2 DMC

• 3 other identifiers: 13684NIH Grant Number-R21DK077372IND Number-54,041
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This year-long investigator-initiated study is designed to determine effects of MK-0677, a GH secretagogue, in renal patients. It is a double-blind, placebo-controlled trial employing the following procedures: Informed consent process, followed by evaluation and screening tests to confirm patients' eligibility. Patients whose screening laboratory results for glycated hemoglobin level, thyroid function, or liver function exceed protocol eligibility criteria will not be randomized. Other exclusions are Congestive Heart Failure Class III or IV by the New York Heart Assocation's (NYHA) Guidelines and specified cardiovascular disorders within six months of baseline visit and muscle weakness associated with neuromuscular or neurological disorders. Before the subject begins taking the experimental drug MK-0677 or placebo, baseline assessments of subjects' hormone and cytokine levels, physical condition, body mass (determined by a DEXA scan), strength and functionality, and appetite will be obtained. In addition, quality of life assessments (SF-36) will be administered. This study's primary outcome is an increase in lean body weight. Secondary outcomes are cytokine and hormone levels, including, leptin, insulin, ghrelin, TNF- alpha, CRPs, IL-1, IL-6, and IL-10, ghrelin associated esterase and adiponectin, nutritional status, quality of life (QoL), food appreciation, physical function and economic impact. 70 subjects will be the enrollment target. This number was determined to offset projected screen failure and early withdrawal rates, and to ensure that 42 subjects complete the study.

Conditions

Chronic Kidney Disease; Kidney Disease

Keywords

Kidney Disease; Chronic Kidney Disease; Growth Hormone

Outcome Measures

Primary Outcomes (1)

• Lean body weight.

  N/A - Study Withdrawn

  12 months

Secondary Outcomes (5)

• Cytokine levels

  12 months

• Hormone levels

  12 months

• Nutritional status

  12 months

• Quality of life

  12 months

• Physical function

  12 months

Study Arms (2)

MK-0677

EXPERIMENTAL

The oral agent MK-677 is spiropiperidine, Merck L-163 191, GH secretagogue ghrelin mimetic which increases GH and IGF-I secretion, fat free mass and energy expenditure76-79. It is produced by Merck \& Co, Inc.

Drug: MK-0677

Placebo

PLACEBO COMPARATOR

Inactive Pill used as a comparator

Drug: Placebo

Interventions

MK-0677 DRUG

The oral agent MK-677 is spiropiperidine, Merck L-163 191, GH secretagogue ghrelin mimetic which increases GH and IGF-I secretion, fat free mass and energy expenditure76-79. It is produced by Merck \& Co, Inc.

MK-0677

Placebo DRUG

Inactive Pill used as a comparator

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female age 18 to 85.
• GFR by the MDRD estimate ≤ 30 ml/minute/ 1.73m2 at two consecutive determinations (one GFR result from the screening visit labs and another GFR result from a prior laboratory determination and/or an unscheduled visit to confirm that the GFR is truly within the correct range.)

You may not qualify if:

• Prior use of experimental drug, MK-0677
• Subject has been diagnosed with neuromuscular or neurological disease causing muscle weakness.
• Body mass index greater than 35 kg/m2, or morbid obesity
• Uncontrolled hypothyroidism, defined as an elevated serum thyroid stimulating hormone (TSH) and a free serum thyroxine (T4) less than the lower limit of normal, when tested at screening (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 screening
• Hemoglobin \< 10 Gm/dl at screening
• Elevated serum transaminases (alanine transaminase (ALT) and aspartate transaminase (AST). (≥2.0 times the upper limit of normal at screening)
• Elevated alkaline phosphatase (Alk Phos). (≥3.0 times the upper limit of normal at screening)
• Diabetes with one or more of the following:
• Poorly controlled diabetes as defined by a HbA1C \>7.0% at screening
• Pre-proliferative and Proliferative diabetic retinopathy \[To participate in this study, diabetic patients will need to have had a dilated ophthalmology exam or retinal photography within 12 months of enrollment. Individuals who already have extensive background retinopathy will need to have a dilated ophthalmology exam within the 3 months of enrollment. Patients with pre-proliferative or proliferative retinopathy will be excluded.\]
• Unwilling or unable to check blood glucose at home at least daily
• Currently receiving a systemic corticosteroid dose of ≥10 mg prednisone. (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.

Sponsors & Collaborators

• University of Virginia: lead
• National Institutes of Health (NIH): collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Kidney Diseases

Interventions

ibutamoren mesylate

Condition Hierarchy (Ancestors)

Renal Insufficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Warren K. Bolton, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 29, 2010
• First Posted: April 28, 2011
• Study Start: March 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: May 14, 2018

Record last verified: 2012-04

Locations

US (1)