Back to results

Ghrelin Dose Finding In Frail Elderly

Primary Purpose

The Frailty Syndrome

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Ghrelin Group 1

Ghrelin Group 2

About this trial

This is an interventional other trial for The Frailty Syndrome

Eligibility Criteria

70 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

We will include men and women aged 70 or older who are able to provide informed consent and are frail by the Fried criteria (Table 1).
Table 1. Frailty criteria. Individuals with three, four, or all five criteria are frail.
Weight loss: Unintentional weight loss of >5% over the previous year

Exhaustion: Two statements are read:

I felt that everything I did was an effort
I could not get going. The question is asked "How often in the last week did you feel this way?" 0 = rarely or none of the time (<1 day), 1 = some or a little of the time (1-2 days), 2 = a moderate amount of the time (3-4 days), or 3 = most of the time. A "2" or "3" response to either question is a positive response.
- Low physical activity: Kcal/week of physical activity calculated from the short version of the Minnesota Leisure Time Activity questionnaire.40 < 383 kcals in men or < 270 kcals/wk in women is positive for this criterion.
- Slow walking speed: A usual pace, 15-ft walk timed from a defined standing start. For men ≤173 cm tall and women ≤159 cm, ≥7 sec, and for men >173 cm and women > 159 cm, ≥ 6 sec is positive for this criterion.
- Weakness: Hand grip strength measured with a dynamometer. The average of three measurements performed in the dominant hand is used. For men with BMI ≤ 24 kg/m2, the cutoff is ≤ 29 kg, for BMI 24.1 to 26 the cutoff is ≤ 30 kg, for BMI 26.1 to 28 the cutoff is ≤30 kg, and for BMI > 28 the cutoff is ≤ 32 kg. For women with BMI ≤ 23 kg/m2, the cutoff is ≤ 17 kg, for BMI 23.1 to 26 the cutoff is ≤ 17.3 kg, for BMI 26.1 to 29 the cutoff is ≤ 18 kg, and for BMI > 29 the cutoff is ≤ 21 kg for a positive criterion.

Exclusion Criteria:

Diabetes mellitus or fasting glucose ≥ 126 mg/dL
Hospitalization for stroke, myocardial infarction, coronary artery bypass graft surgery, vascular surgery in the past six months.
NYHA Class III or IV congestive heart failure
Therapy for cancer in the past 12 months, except non-melanoma skin cancer
BMI≥ 30 kg/m2
Current use of corticosteroids other than topical, ophthalmic, and inhaled preparations
Therapy with megestrol acetate or dronabinol within the last 6 weeks
TSH measured as <0.4 mU/L or greater than 10mU/L
Abnormal liver function tests (LFTs > 2x upper limit of normal)
Hemoglobin < 11g/dL
Insulin-like growth factor-I (IGF-I) above the age-specific reference range
History of surgery within the last 30 days
Unstable medical or psychological conditions or unstable home or food environment
Cognitive deficit as defined by a Folstein Mini Mental State Exam score < 18/30
Depression (defined as a score of >11 on the Geriatric Depression Questionnaire)
-

Sites / Locations

Clinical and Translational Research Center, University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Ghrelin Group 1

Ghrelin Group 2

Arm Description

Dose finding with each of the first two participant coming to the CTRC for four visits greater than or equal to 72 hours apart and on each receiving subcutaneous injection of - placebo (first visit) and three escalating doses of ghrelin 2ug/kg (second visit) , 5 ug/kg (third visit), and 10 ug/kg (fourth visit).

Dose finding with each of the final three participant coming to the CTRC for four visits greater than or equal to 72 hours apart and on each receiving subcutaneous injection of - placebo (first visit) and three escalating doses of ghrelin 5ug/kg (second visit) , 7.5 ug/kg (third visit), and 10 ug/kg (fourth visit).

Outcomes

Primary Outcome Measures

Treatment Emergent Adverse Events

Number and type of treatment emergent adverse events

Median Energy Intake

Median energy intake at breakfast, which was served 30 minutes post-placebo or ghrelin administration demonstrated at each dose level.

Percentage of Total Energy Intake Relative to Placebo

% of total energy relative to placebo - breakfast served 30 minutes post-placebo or ghrelin administration.

Growth Hormone

median growth hormone peak 30 minutes after placebo/ghrelin.

Cortisol Level

Cortisol response to ghrelin or placebo - levels at 0, 60 and 120 minutes after dosing

Glucose Levels

Median fasting and peak postprandial Glucose levels (60 or 90 minutes from dosing) at placebo and at each ghrelin dose.

Insulin Level

Median fasting insulin levels at baseline and 90 minutes after dosing

Free Fatty Acid Level

Free Fatty Acid levels (mEq/L) at 60 and 90 minutes after meal (90 and 120 minutes)

Secondary Outcome Measures

Full Information

NCT ID

NCT01605435

First Posted

May 22, 2012

Last Updated

November 26, 2019

Sponsor

University of Pennsylvania

1. Study Identification

Unique Protocol Identification Number

NCT01605435

Brief Title

Ghrelin Dose Finding In Frail Elderly

Official Title

Ghrelin In Frail Elderly Subcutaneous Dose Finding Study

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Completed

Study Start Date

May 2012 (undefined)

Primary Completion Date

December 2012 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Pennsylvania

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Frailty is a geriatric syndrome leading to physical deterioration including muscle wasting (sarcopenia) and unintentional weight loss. There are currently no approved therapies for frailty. Ghrelin is a hormone produced by the stomach that stimulates appetite centers in the brain. The purpose of this study is to determine the optimal subcutaneous ghrelin dose as a potential intervention for frail elderly individuals. We will examine food intake and metabolic parameters after placebo and ghrelin administration at three escalating subcutaneously administered doses.

Detailed Description

This study is to determine the optimal ghrelin dose for use in a daily subcutaneous dosing study in frail individuals. Using data from our previous study and the published literature, we have designed a single blind, single dose administration study in which we will examine food intake after ghrelin administration and metabolic parameters (plasma glucose, insulin, free fatty acids, and cortisol) pre and post ghrelin administration.We have selected a dose range using our own and previously published studies from which we will determine subcutaneous doses to use in subsequent studies. The selection criteria for subsequent studies will be the dose that maximizes food intake by more than 30% without inducing hyperglycemia or raising cortisol levels. Participants must meet all inclusion criteria and have no exclusion criteria. Data will be analyzed after the first three participants have completed the protocol and used to inform dose modifications for the next three participants. Data from this portion of the study will be analyzed immediately after its completion, to allow updates to the design of the next study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

The Frailty Syndrome

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Non-Randomized

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ghrelin Group 1

Arm Type

Experimental

Arm Description

Arm Title

Ghrelin Group 2

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ghrelin Group 1

Other Intervention Name(s)

First dose escalation group

Intervention Description

The first two participants received placebo at baseline visit, 2 mcg/kg as a single subcutaneous dose at Visit 2, 5 mcg/kg as a single subcutaneous dose at Visit 3, and 10 mcg/Kg as a single subcutaneous dose at visit 4. There was 3-10 days between visits.

Intervention Type

Drug

Intervention Name(s)

Ghrelin Group 2

Other Intervention Name(s)

Second dose escalation group

Intervention Description

The next three participants received placebo at baseline visit, 5 mcg/kg as a single subcutaneous dose at Visit 2, 7.5 mcg/kg as a single subcutaneous dose at Visit 3, and 10 mcg/Kg as a single subcutaneous dose at visit 4.

Primary Outcome Measure Information:

Title

Treatment Emergent Adverse Events

Description

Number and type of treatment emergent adverse events

Time Frame

30 days following the last administration of study treatment.

Title

Median Energy Intake

Description

Median energy intake at breakfast, which was served 30 minutes post-placebo or ghrelin administration demonstrated at each dose level.

Time Frame

30 mins post-ghrelin or placebo

Title

Percentage of Total Energy Intake Relative to Placebo

Description

% of total energy relative to placebo - breakfast served 30 minutes post-placebo or ghrelin administration.

Time Frame

30 mins post-ghrelin or placebo

Title

Growth Hormone

Description

median growth hormone peak 30 minutes after placebo/ghrelin.

Time Frame

30 minutes after ghrelin administration

Title

Cortisol Level

Description

Cortisol response to ghrelin or placebo - levels at 0, 60 and 120 minutes after dosing

Time Frame

0, 60 and 120 minutes after dosing

Title

Glucose Levels

Description

Median fasting and peak postprandial Glucose levels (60 or 90 minutes from dosing) at placebo and at each ghrelin dose.

Time Frame

0 minutes (baseline) and 60 or 90 minutes from dosing

Title

Insulin Level

Description

Median fasting insulin levels at baseline and 90 minutes after dosing

Time Frame

0 and 90 minutes after dosing

Title

Free Fatty Acid Level

Description

Free Fatty Acid levels (mEq/L) at 60 and 90 minutes after meal (90 and 120 minutes)

Time Frame

90 and 120 minutes after dosing

10. Eligibility

Sex

All

Minimum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: We will include men and women aged 70 or older who are able to provide informed consent and are frail by the Fried criteria (Table 1). Table 1. Frailty criteria. Individuals with three, four, or all five criteria are frail. Weight loss: Unintentional weight loss of >5% over the previous year Exhaustion: Two statements are read: I felt that everything I did was an effort I could not get going. The question is asked "How often in the last week did you feel this way?" 0 = rarely or none of the time (<1 day), 1 = some or a little of the time (1-2 days), 2 = a moderate amount of the time (3-4 days), or 3 = most of the time. A "2" or "3" response to either question is a positive response. Low physical activity: Kcal/week of physical activity calculated from the short version of the Minnesota Leisure Time Activity questionnaire.40 < 383 kcals in men or < 270 kcals/wk in women is positive for this criterion. Slow walking speed: A usual pace, 15-ft walk timed from a defined standing start. For men ≤173 cm tall and women ≤159 cm, ≥7 sec, and for men >173 cm and women > 159 cm, ≥ 6 sec is positive for this criterion. Weakness: Hand grip strength measured with a dynamometer. The average of three measurements performed in the dominant hand is used. For men with BMI ≤ 24 kg/m2, the cutoff is ≤ 29 kg, for BMI 24.1 to 26 the cutoff is ≤ 30 kg, for BMI 26.1 to 28 the cutoff is ≤30 kg, and for BMI > 28 the cutoff is ≤ 32 kg. For women with BMI ≤ 23 kg/m2, the cutoff is ≤ 17 kg, for BMI 23.1 to 26 the cutoff is ≤ 17.3 kg, for BMI 26.1 to 29 the cutoff is ≤ 18 kg, and for BMI > 29 the cutoff is ≤ 21 kg for a positive criterion. Exclusion Criteria: Diabetes mellitus or fasting glucose ≥ 126 mg/dL Hospitalization for stroke, myocardial infarction, coronary artery bypass graft surgery, vascular surgery in the past six months. NYHA Class III or IV congestive heart failure Therapy for cancer in the past 12 months, except non-melanoma skin cancer BMI≥ 30 kg/m2 Current use of corticosteroids other than topical, ophthalmic, and inhaled preparations Therapy with megestrol acetate or dronabinol within the last 6 weeks TSH measured as <0.4 mU/L or greater than 10mU/L Abnormal liver function tests (LFTs > 2x upper limit of normal) Hemoglobin < 11g/dL Insulin-like growth factor-I (IGF-I) above the age-specific reference range History of surgery within the last 30 days Unstable medical or psychological conditions or unstable home or food environment Cognitive deficit as defined by a Folstein Mini Mental State Exam score < 18/30 Depression (defined as a score of >11 on the Geriatric Depression Questionnaire) -

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anne R. Cappola, M.D., Sc.M.

Organizational Affiliation

University Of Pennsylvania, Perelman School of Medicine, Department of Endocrinology, Diabetes and Metabolism

Official's Role

Principal Investigator

Facility Information:

Facility Name

Clinical and Translational Research Center, University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Ghrelin Dose Finding In Frail Elderly

We'll reach out to this number within 24 hrs