HypopituitarismPhase 3GHDNCT01007071
Effects of Growth Hormone on Cognition and Cerebral Metabolism in Adults With Growth Hormone Deficiency
A Phase 3 study testing Human Growth Hormone (1-134) in people with Hypopituitarism, run by Stanford University at 1 site in United States.
Trial summary
Patients with Growth hormone (GH) deficiency often report impaired quality of life and difficulty with mental functioning. It has been suggested that GH replacement in such patients leads to improvement in cognitive function. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hypopituitarism
- What is being tested?
- Human Growth Hormone (1-134)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2009to 12 Dec 2012
- Phase
- Phase 3
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to provide written informed consent and comply with study assessments for the full duration of the study
- Age 18-65 years old
- Both men and women
- Naive to GH replacement therapy
- Diagnosis of Growth Hormone deficiency, adult onset
- Good general health
- Normal thyroid, adrenal or gonadal function, or stable thyroid, glucocorticoid (at replacement doses) and gonadal replacement therapy for at least 3 months prior to study initiation. If subjects are receiving transdermal testosterone, attainment of mid-normal serum values will be considered adequate. If subjects are on intramuscular testosterone, attainment of mid-normal serum testosterone at mid-injection cycle will be considered adequate
Who cannot join
- Pregnancy (positive pregnancy test) prior to enrollment in the study
- Any other condition that the investigator believes would pose a significant hazard to the subject if Growth Hormone therapy was initiated
- Idiopathic Growth Hormone Deficiency
- DSM IV diagnosis of Major Depressive Disorder with or without psychotic features, Bipolar II Disorder with or without psychotic features in a major depressive episode
- Current use of psychotropic medications
- History of moderate to severe brain injury
Show all 16Show fewer
- Clinically significant cardiovascular disease
- Anemia with hct<30
- Renal insufficiency with creatinine >2.0
- Recent history of excessive alcohol use
- Participation in another simultaneous medical investigation or trial
- Active neoplasm
- Prader Willi Syndrome
- History of brain radiation
- Chemotherapy, past or present use
- History of head or eye injury involving persistent metal fragments, and implanted electrical device (such as a heart pacemaker)
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: Effects of Growth Hormone on Cognition and Cerebral Metabolism in Adults
Patients with Growth hormone (GH) deficiency often report impaired quality of life and difficulty with mental functioning. It has been suggested that GH replacement in such patients leads to improvement in cognitive function. The aim of this study is to elucidate the effects of GH replacement in patients with GH deficiency on cognitive function using structural and functional neuroimaging and cognitive testing.
Read the detailed description
Eligibility screening: Diagnosis of GHD will be based on standard testing, including a blunted GH response to stimulation with glucagon provocation, defined as GH <3 microgram/l. Subjects with adult-onset GH deficiency will be included if they are age 18-65 years old, naive to GH replacement therapy, in good general health, and on stable thyroid, glucocorticoid (at replacement doses) and gonadal replacement therapy for at least 6 weeks prior to study initiation. Patients with history a Major Depression will be excluded.
Baseline: Qualifying subjects will be admitted to the CTRU for the following: Weight, body mass index, waist/hip ratio, menstrual cycle history on female subjects and vital signs. Initial clinical laboratory assessments will include IGF-1, a complete blood count, liver function tests, free T4, and a serum pregnancy test for women. Subjects will undergo 3 hours of neuropsychological testing when attention, working memory, executive function and verbal memory will be assessed with the Wechsler Adult Intelligence Scale III and Wechsler Memory Scale (WMS III). Quality of life and mood will be quantified through the Quality of Life Scale, Hamilton Rating Scale for Depression and the Quality of Life Assessment of Growth Hormone Deficiency in Adults (Qol AGHDA). After a lunch break, the patients will undergo a 1 hour MRI scan. Resting images will be obtained, and thereafter simple letters, words or pictures will be projected to subjects while in the scanner. The subjects will be asked simple questions relating to these stimuli.
Randomization and treatment: Following completion of the baseline measurements, study participants will be randomized in a double blind fashion to receive either active treatment with GH or placebo for a period of 16 weeks. GH dosages will be increased incrementally over the first 6 weeks. At 16 weeks, all subjects randomized to placebo will be switched to GH in an open label fashion with dose schedules based on the above titration. Subjects initially randomized to GH will continue to receive GH with their endocrinologist without further follow up for the study.
For efficacy measures, neuropsychological testing and fMRI will be performed at baseline and at 16 weeks, and, for subjects initially randomized to placebo, repeat studies will be performed at 32 weeks.
Safety monitoring will include assessment of changes in thyroid and adrenal status, as well as changes in liver function.
- Conditions
- Hypopituitarism
- Being tested
- Human Growth Hormone (1-134), Placebo
- Medical subject headings
- Hypopituitarism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human Growth Hormone (1-134)Drug
Also called Nutropin (brand name)
Subjects randomized to human growth hormone (1-134) for 16 weeks. In this arm, growth hormone is dosed sc on a daily basis and increased over first 6 weeks (Men: start at 0.2 mg sc/d, increase to 0.6 mg sc/d after 4 weeks. Women, postmenopausal: start at 0.3 mg sc/d, increase to 0.9 mg sc/d after 4 weeks. Women premenopausal or on estrogen: start at 0.6 mg sc/d, increase to 1.3 mg sc/d after 4 weeks.) Dose adjustments based on serum IGF-1 levels at 6 and 12 weeks, with final IGF-1 measurement for efficacy performed at 16 weeks, with goal in range of -0.5 SD to +2SD. An elevated serum IGF-1 value will result in a 20% dose reduction in GH in an active and random placebo patient. Similarly, a low serum IGF-1 will result in a 20% dose increase in an active and random placebo subject.
PlaceboDrug
Subjects randomized to placebo
| Study group | Role | What they receive |
|---|---|---|
| Growth hormone | Experimental | Subjects randomized to growth hormone (1-134) for 16 weeks. In this arm, growth hormone is dosed sc on a daily basis and increased over first 6 weeks (Men: start at 0.2 mg sc/d, increase to 0.6 mg sc/d after 4 weeks. Women, postmenopausal: start at 0.3 mg sc/d, increase to 0.9 mg sc/d after 4 weeks. Dose adjustments based on serum insulin-like growth factor-1 (IGF-1) levels at 6 and 12 weeks, with final IGF-1 measurement for efficacy performed at 16 weeks, with goal in range of -0.5 standard deviation (SD) to +2SD. An elevated serum IGF-1 value will result in a 20% dose reduction in GH in an active and random placebo patient. Similarly, a low serum IGF-1 will result in a 20% dose increase in an active and random placebo subject. Receives: Drug: Human Growth Hormone (1-134) |
| Placebo | Placebo comparator | Subjects randomized to placebo for 16 weeks. As noted above, placebo subjects will be initiated on a daily subcutaneous injection, with dose changes based on changes in active drug subjects. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
BOLD Signal Measured by Functional MRI Scan to Functional Connectivity Measured by fMRI
Functional MRI scans were to be performed at baseline and at 16 weeks. Changes in functional connectivity before and after 16 weeks of treatment were analyzed. The analysis involved approximately 40,000 paired sample t-tests. The dependent variable here for each subject is the correlation between the BOLD timeseries in the seed region (posterior cingulate cortex) and the BOLD timeseries in a given, standard space, brain voxel. This paired-sample t-test is run, separately, for every voxel in the brain. The pre-specified Outcome Measure intended to report the number of voxels that showed significant changes with active treatment. A preliminary analysis was conducted using a paired-sample t-test at each of the 40,000+ voxels, however, none of the voxels reached the level of significance. Since no significant voxels were detected, subsequent planned analyses were not performed, and summary level data cannot be reported for this Outcome Measure.
Measured: Baseline and 16 weeks
Secondary outcomes (1)
Neuropsychological Testing of Executive Function
Executive function was assessed in part B of the 2-part Trail Making Test. In Part A, 25 circles are distributed over a sheet of paper, numbered 1 - 25, and the patient draws lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1-13) and letters (A-L); as in Part A, the patient draws lines to connect the circles in an ascending pattern, but with the added task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.). The patient is instructed to connect the circles as quickly as possible. The amount of time the patient takes to connect the circles is recorded as their score. If patients make an error, they are corrected then continue from the last correct circle. The number of seconds for completion of part B is reported, therefore higher scores reveal greater impairment.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2009 (estimated)
- Study start1 Nov 2009
- Primary completion12 Dec 2012
- Study completion12 Dec 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 HypopituitarismStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Laurence Katznelson, Stanford University
- Investigators
- Era Sidhaye Shah, Sub-investigator, Stanford UniversityLaurence Katznelson, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01007071
- Sponsor's protocol ID
- SU-10022009-4140
- Other IDs
- IRB eprotocol # 15129
- Acronym
- GHD
- Status last verified
- Oct 2017
- First submitted
- 30 Oct 2009
- Last updated
- 17 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Growth Hormone on Cognition and Cerebral Metabolism in Adults
- ClinicalTrials.gov ID
- NCT01007071
- Acronym / sponsor ID
- GHD / SU-10022009-4140
- Conditions
- Hypopituitarism
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 1 Nov 2009 (actual)
- Primary completion
- 12 Dec 2012 (actual)
- Study completion
- 12 Dec 2012 (actual)
- First posted
- 3 Nov 2009 (estimated)
- Results
- Posted 17 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with Growth hormone (GH) deficiency often report impaired quality of life and difficulty with mental functioning. It has been suggested that GH replacement in such patients leads to improvement in cognitive function. The aim of this study is to elucidate the effects of GH replacement in patients with GH deficiency on cognitive function using structural and functional neuroimaging and cognitive testing.
Detailed description
Eligibility screening: Diagnosis of GHD will be based on standard testing, including a blunted GH response to stimulation with glucagon provocation, defined as GH <3 microgram/l. Subjects with adult-onset GH deficiency will be included if they are age 18-65 years old, naive to GH replacement therapy, in good general health, and on stable thyroid, glucocorticoid (at replacement doses) and gonadal replacement therapy for at least 6 weeks prior to study initiation. Patients with history a Major Depression will be excluded.
Baseline: Qualifying subjects will be admitted to the CTRU for the following: Weight, body mass index, waist/hip ratio, menstrual cycle history on female subjects and vital signs. Initial clinical laboratory assessments will include IGF-1, a complete blood count, liver function tests, free T4, and a serum pregnancy test for women. Subjects will undergo 3 hours of neuropsychological testing when attention, working memory, executive function and verbal memory will be assessed with the Wechsler Adult Intelligence Scale III and Wechsler Memory Scale (WMS III). Quality of life and mood will be quantified through the Quality of Life Scale, Hamilton Rating Scale for Depression and the Quality of Life Assessment of Growth Hormone Deficiency in Adults (Qol AGHDA). After a lunch break, the patients will undergo a 1 hour MRI scan. Resting images will be obtained, and thereafter simple letters, words or pictures will be projected to subjects while in the scanner. The subjects will be asked simple questions relating to these stimuli.
Randomization and treatment: Following completion of the baseline measurements, study participants will be randomized in a double blind fashion to receive either active treatment with GH or placebo for a period of 16 weeks. GH dosages will be increased incrementally over the first 6 weeks. At 16 weeks, all subjects randomized to placebo will be switched to GH in an open label fashion with dose schedules based on the above titration. Subjects initially randomized to GH will continue to receive GH with their endocrinologist without further follow up for the study.
For efficacy measures, neuropsychological testing and fMRI will be performed at baseline and at 16 weeks, and, for subjects initially randomized to placebo, repeat studies will be performed at 32 weeks.
Safety monitoring will include assessment of changes in thyroid and adrenal status, as well as changes in liver function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Growth hormone | Experimental | Drug: Human Growth Hormone (1-134)Subjects randomized to growth hormone (1-134) for 16 weeks. In this arm, growth hormone is dosed sc on a daily basis and increased over first 6 weeks (Men: start at 0.2 mg sc/d, increase to 0.6 mg sc/d after 4 weeks. Women, postmenopausal: start at 0.3 mg sc/d, increase to 0.9 mg sc/d after 4 weeks. Dose adjustments based on serum insulin-like growth factor-1 (IGF-1) levels at 6 and 12 weeks, with final IGF-1 measurement for efficacy performed at 16 weeks, with goal in range of -0.5 standard deviation (SD) to +2SD. An elevated serum IGF-1 value will result in a 20% dose reduction in GH in an active and random placebo patient. Similarly, a low serum IGF-1 will result in a 20% dose increase in an active and random placebo subject. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects randomized to placebo for 16 weeks. As noted above, placebo subjects will be initiated on a daily subcutaneous injection, with dose changes based on changes in active drug subjects. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Ability to provide written informed consent and comply with study assessments for the full duration of the study
- Age 18-65 years old
- Both men and women
- Naive to GH replacement therapy
- Diagnosis of Growth Hormone deficiency, adult onset
Key exclusion criteria (16 listed)
- Pregnancy (positive pregnancy test) prior to enrollment in the study
- Any other condition that the investigator believes would pose a significant hazard to the subject if Growth Hormone therapy was initiated
- Idiopathic Growth Hormone Deficiency
- DSM IV diagnosis of Major Depressive Disorder with or without psychotic features, Bipolar II Disorder with or without psychotic features in a major depressive episode
- Current use of psychotropic medications
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 |
|---|---|---|
| Human Growth Hormone (1-134)Also: Nutropin (brand name)Subjects randomized to human growth hormone (1-134) for 16 weeks. In this arm, growth hormone is dosed sc on a daily basis and increased over first 6 weeks (Men: start at 0.2 mg sc/d, increase to 0.6 mg sc/d after 4 weeks. Women, postmenopausal: start at 0.3 mg sc/d, increase to 0.9 mg sc/d after 4 weeks. Women premenopausal or on estrogen: start at 0.6 mg sc/d, increase to 1.3 mg sc/d after 4 weeks.) Dose adjustments based on serum IGF-1 levels at 6 and 12 weeks, with final IGF-1 measurement for efficacy performed at 16 weeks, with goal in range of -0.5 SD to +2SD. An elevated serum IGF-1 value will result in a 20% dose reduction in GH in an active and random placebo patient. Similarly, a low serum IGF-1 will result in a 20% dose increase in an active and random placebo subject. | Drug | Growth hormone |
| PlaceboSubjects randomized to placebo | Drug | Placebo |
Primary outcome
BOLD Signal Measured by Functional MRI Scan to Functional Connectivity Measured by fMRI
Time frame: Baseline and 16 weeks
Functional MRI scans were to be performed at baseline and at 16 weeks. Changes in functional connectivity before and after 16 weeks of treatment were analyzed. The analysis involved approximately 40,000 paired sample t-tests. The dependent variable here for each subject is the correlation between the BOLD timeseries in the seed region (posterior cingulate cortex) and the BOLD timeseries in a given, standard space, brain voxel. This paired-sample t-test is run, separately, for every voxel in the brain. The pre-specified Outcome Measure intended to report the number of voxels that showed significant changes with active treatment. A preliminary analysis was conducted using a paired-sample t-test at each of the 40,000+ voxels, however, none of the voxels reached the level of significance. Since no significant voxels were detected, subsequent planned analyses were not performed, and summary level data cannot be reported for this Outcome Measure.
1 secondary outcome
Neuropsychological Testing of Executive Function
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Era Sidhaye Shah sub-investigator
Stanford University
Laurence Katznelson principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Human Growth Hormone (1-134) in people with Hypopituitarism, run by Stanford University 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 7 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 17 Nov 2017. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 17 Nov 2017). 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?
BOLD Signal Measured by Functional MRI Scan to Functional Connectivity Measured by fMRI (time frame: Baseline and 16 weeks). 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 17 Nov 2017.