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

May 8, 2018 updated by: Warren K Bolton, University of Virginia

A Phase 2, Investigator-Initiated, Randomized, Double-Blind, Placebo-Controlled Study to Determine Growth Hormone Secretagogue MK-0677's Effect on Lean Body Mass in Chronic Kidney Disease Subjects With Stage 4 and Stage 5 Kidney Disease

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 81 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.)

Exclusion Criteria:

  • 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:

    1. Poorly controlled diabetes as defined by a HbA1C >7.0% at screening
    2. 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.]
    3. 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.

  • 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 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. (a drug screen will not be done, this information will be obtained by history)
  • Patient plans to relocate 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.
  • If female, patient must not be pregnant or nursing. Patient must be postmenopausal, surgically sterilized, or willing to take adequate contraceptive precautions (i.e. use double barrier methods).
  • HIV positive (medical history review and patient report)
  • Patient is on potent CYP3A4 Inhibitor or Inducer Drugs within one week of starting study drug

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: MK-0677
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
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.
Placebo Comparator: Placebo
Inactive Pill used as a comparator
Drug: Placebo
Inactive Pill used as a comparator

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Lean body weight.
Time Frame: 12 months
N/A - Study Withdrawn
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cytokine levels
Time Frame: 12 months
N/A - Study Withdrawn
12 months
Hormone levels
Time Frame: 12 months
N/A - Study Withdrawn
12 months
Nutritional status
Time Frame: 12 months
N/A - Study Withdrawn
12 months
Quality of life
Time Frame: 12 months
N/A - Study Withdrawn
12 months
Physical function
Time Frame: 12 months
N/A - Study Withdrawn
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Virginia

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC
National Institutes of Health (NIH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Warren K. Bolton, MD, University of Virginia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 29, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 26, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 28, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 14, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 8, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 13684
  • NIH Grant Number-R21DK077372
  • IND Number-54,041

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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