The Frailty SyndromePhase 2NCT01605435
Ghrelin Dose Finding In Frail Elderly
A Phase 2 study testing Ghrelin Group 1 and Ghrelin Group 2 in people with The Frailty Syndrome, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- The Frailty Syndrome
- What is being tested?
- Ghrelin Group 1 and Ghrelin Group 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- May 2012to Dec 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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)
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical and Translational Research Center, University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Ghrelin In Frail Elderly Subcutaneous Dose Finding Study
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.
Read the 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.
- Conditions
- The Frailty Syndrome
- Being tested
- Ghrelin Group 1, Ghrelin Group 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ghrelin Group 1Drug
Also called First dose escalation group
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.
Ghrelin Group 2Drug
Also called Second dose escalation group
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.
| Study group | Role | What they receive |
|---|---|---|
| Ghrelin Group 1 | Experimental | 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). Receives: Drug: Ghrelin Group 1 |
| Ghrelin Group 2 | Experimental | 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). Receives: Drug: Ghrelin Group 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Emergent Adverse Events
Number and type of treatment emergent adverse events
Measured: 30 days following the last administration of study treatment.
Median Energy Intake
Median energy intake at breakfast, which was served 30 minutes post-placebo or ghrelin administration demonstrated at each dose level.
Measured: 30 mins post-ghrelin or placebo
Percentage of Total Energy Intake Relative to Placebo
% of total energy relative to placebo - breakfast served 30 minutes post-placebo or ghrelin administration.
Measured: 30 mins post-ghrelin or placebo
Growth Hormone
median growth hormone peak 30 minutes after placebo/ghrelin.
Measured: 30 minutes after ghrelin administration
Cortisol Level
Cortisol response to ghrelin or placebo - levels at 0, 60 and 120 minutes after dosing
Measured: 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.
Measured: 0 minutes (baseline) and 60 or 90 minutes from dosing
Insulin Level
Median fasting insulin levels at baseline and 90 minutes after dosing
Measured: 0 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)
Measured: 90 and 120 minutes after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2012 (estimated)
- Study startMay 2012
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for The Frailty SyndromeStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anne Cappola, University of Pennsylvania
- Investigators
- Anne R. Cappola, M.D., Sc.M., Principal investigator, University Of Pennsylvania, Perelman School of Medicine, Department of Endocrinology, Diabetes and Metabolism
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01605435
- Sponsor's protocol ID
- IRB 814309
- Status last verified
- Nov 2019
- First submitted
- 22 May 2012
- Last updated
- 12 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ghrelin In Frail Elderly Subcutaneous Dose Finding Study
- ClinicalTrials.gov ID
- NCT01605435
- Acronym / sponsor ID
- IRB 814309
- Conditions
- The Frailty Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 24 May 2012 (estimated)
- Results
- Posted 10 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ghrelin Group 1 | Experimental | Drug: Ghrelin Group 1Dose 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). |
| Ghrelin Group 2 | Experimental | Drug: Ghrelin Group 2Dose 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). |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (9 listed)
- 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
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ghrelin Group 1Also: First dose escalation groupThe 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. | Drug | Ghrelin Group 1 |
| Ghrelin Group 2Also: Second dose escalation groupThe 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. | Drug | Ghrelin Group 2 |
Primary outcome
Treatment Emergent Adverse Events
Time frame: 30 days following the last administration of study treatment.
Number and type of treatment emergent adverse events
Median Energy Intake
Time frame: 30 mins post-ghrelin or placebo
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
Time frame: 30 mins post-ghrelin or placebo
% of total energy relative to placebo - breakfast served 30 minutes post-placebo or ghrelin administration.
Growth Hormone
Time frame: 30 minutes after ghrelin administration
median growth hormone peak 30 minutes after placebo/ghrelin.
Cortisol Level
Time frame: 0, 60 and 120 minutes after dosing
Cortisol response to ghrelin or placebo - levels at 0, 60 and 120 minutes after dosing
Glucose Levels
Time frame: 0 minutes (baseline) and 60 or 90 minutes from dosing
Median fasting and peak postprandial Glucose levels (60 or 90 minutes from dosing) at placebo and at each ghrelin dose.
Insulin Level
Time frame: 0 and 90 minutes after dosing
Median fasting insulin levels at baseline and 90 minutes after dosing
Free Fatty Acid Level
Time frame: 90 and 120 minutes after dosing
Free Fatty Acid levels (mEq/L) at 60 and 90 minutes after meal (90 and 120 minutes)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Safety and Tolerability Study of Mesenchymal Stem Cells, HeXell-2020, in Elderly Subjects With Mild to Moderate Frailty Syndrome
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne R. Cappola, M.D., Sc.M. principal investigator
University Of Pennsylvania, Perelman School of Medicine, Department of Endocrinology, Diabetes and Metabolism
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ghrelin Group 1 and Ghrelin Group 2 in people with The Frailty Syndrome, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Emergent Adverse Events (time frame: 30 days following the last administration of study treatment.). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2019.