Human Immunodeficiency Virus-Associated Adipose Redistribution Syndrome
Conditions
Keywords
Serostim, HARS
Brief summary
In Serono Study 24380, the antecedent protocol to Study 25373, patients were randomly assigned in a 3.0-to-1.0 ratio to Groups A and B. All patients in Group A received recombinant human growth hormone (Serostim®) 4 mg daily (the induction phase) for the first 12 weeks, and then were re-randomized to receive either placebo or Serostim 2 mg on alternate days (roughly equivalent to 1 mg daily) during Weeks 12-36 (the maintenance phase). All patients in Group B initially received placebo from baseline to Week 24, and then received Serostim® 4 mg daily from Weeks 24 to 36 (Grunfeld, 2007). In the follow-up Study 25373, any subject who was enrolled in Serono Study 24380 and was assigned to Group A, who fully completed all study visits without a major protocol violation, was eligible to enroll to receive re-treatment with Serostim at a dose of 4 mg daily for 12 weeks. During study 25373, safety was monitored by recording of adverse events and measurement of urinalysis and laboratory blood tests to assess fasting glucose, fasting insulin, and routine biochemistry and hematology parameters. At Week 12 or at the time of study termination, subjects underwent re-assessment of body composition via anthropometry measurements and dual photon absorptiometry (DXA) scanning. In addition, at study termination, measurements of insulin-like growth factor I (IGF-I), insulin-like growth binding protein 3 (IGFBP-3), fasting lipid profile, and oral glucose tolerance testing were obtained.
Interventions
BIOLOGICALSerostim
Serostim® 4 mg daily given for 12 weeks (following a prior 36-week treatment \[Serono Study 24380\] with Serostim® 4 mg daily given for 12 weeks, followed by 24-weeks of either Serostim® 2 mg every other day or Placebo every other day)
Sponsors
EMD Serono
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must meet all inclusion/
Exclusion criteria
for Serono Study 25373, have participated in Serono Study 24380, must have been assigned to Group A, must have completed all treatments and procedures (including baseline, Week 12 and Week 36 Computerized Tomography (CT) and Dual-Energy X-ray Absorptiometry (DXA) Scans) and had no major protocol violation. * Must be taking antiretroviral medications that are approved or are available under a Treatment Investigational New Drug (IND). Subjects must also agree not to discontinue or to change their regimen for the duration of the study except as judged medically necessary. * Must be willing and able to comply with the protocol for the duration of the study. * Must have voluntarily provided written informed consent and a subject authorization under Health Insurance Portability and Accountability Act of 1996 (HIPAA), prior to any study-related procedure that is not part of normal medical care, and with the understanding that the subject may withdraw consent at any time without prejudice to future medical care. * If female, subjects must either: * Be post menopausal (=/\>1 year) or surgically sterilized (i.e., have undergone tubal ligation or hysterectomy), or * Use a contraceptive method for the duration of the study such as: hormonal contraceptive,intra uterine device,diaphragm with spermicide, or condom with spermicide, and * Must be neither pregnant nor breast feeding. * Confirmation that female subjects of childbearing potential are not pregnant must be established by a negative pregnancy test prior to initiating first treatment. A pregnancy test is not required if the subject is post menopausal or surgically sterilized.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline to Week 12 in Trunk Fat as Assessed by Dual-Energy X-Ray Absorptiometry (DXA) Scan | baseline to 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Waist Circumference | baseline to 12 weeks | Measured by anthropometry |
| Change From Baseline to Week 12 in Insulin-like Growth Factor I | baseline to 12 weeks | Circulating levels of IGF-I |
| Oral Glucose Tolerance Testing - Change From Baseline to Week 12 in Fasting Insulin | baseline to 12 weeks | Oral glucose tolerance testing |
| Oral Glucose Tolerance Testing - Change From Baseline to Week 12 in 120 Minute Glucose | baseline to 12 weeks | Oral glucose testing |
| Oral Glucose Tolerance Testing - Change From Baseline to Week 12 in Fasting Glucose | baseline to 12 weeks | Oral glucose testing |
Countries
Canada, United States
Participant flow
Recruitment details
Study Initiation Date: 03 Feb 2005 (date of first subject, first dose) Study Completion Date 04 Jan 2006 (date of last subject, last visit) 26 study centers in the United States and British Columbia participated in this study, with each center enrolling at least one subject into the study.
Pre-assignment details
Any subject who was enrolled in Serono Study 24380, assigned to Group A, and fully completed all study visits without major protocol violations was to be allowed to enroll in Study 25373
Participants by arm
| Arm | Count |
|---|---|
| Serostim Serostim® 4 mg daily given for 12 weeks (following a prior 36-week treatment \[Serono Study 24380\] with Serostim® 4 mg daily given for 12 weeks, followed by 24-weeks of either Serostim® 2 mg every other day or Placebo every other day) | 126 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Reason unspecified | 1 |
| Overall Study | Subject decision | 1 |
Baseline characteristics
| Characteristic | Serostim |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 126 Participants |
| Age Continuous | 45.4 years STANDARD_DEVIATION 7.1 |
| Insulin-like Growth Factor I | 242.6 ng/mL STANDARD_DEVIATION 132.8 |
| Oral Glucose Tolerance Testing - 120 Minute Glucose | 102.3 mg/dL STANDARD_DEVIATION 35.7 |
| Oral Glucose Tolerance Testing - Fasting Glucose | 94.5 mg/dL STANDARD_DEVIATION 14.7 |
| Oral Glucose Tolerance Testing - Fasting Insulin | 11.4 mcIU/mL STANDARD_DEVIATION 13.6 |
| Region of Enrollment Canada | 1 participants |
| Region of Enrollment United States | 125 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 113 Participants |
| Trunk Fat | 10.4 kg STANDARD_DEVIATION 4.9 |
| Waist Circumference | 97.3 cm STANDARD_DEVIATION 9.6 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 89 / 126 |
| serious Total, serious adverse events | 2 / 126 |
Outcome results
Primary
Change From Baseline to Week 12 in Trunk Fat as Assessed by Dual-Energy X-Ray Absorptiometry (DXA) Scan
Time frame: baseline to 12 weeks
Population: The analysis population reported here comprised the subjects who received at least one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Serostim | Change From Baseline to Week 12 in Trunk Fat as Assessed by Dual-Energy X-Ray Absorptiometry (DXA) Scan | -1.7 kg | Standard Deviation 1.4 |
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline to Week 12 in Insulin-like Growth Factor I
Circulating levels of IGF-I
Time frame: baseline to 12 weeks
Population: The analysis population reported here comprised the subjects who received at least one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Serostim | Change From Baseline to Week 12 in Insulin-like Growth Factor I | 135.7 ng/mL | Standard Deviation 210.7 |
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline to Week 12 in Waist Circumference
Measured by anthropometry
Time frame: baseline to 12 weeks
Population: The analysis population reported here comprised the subjects who received at least one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Serostim | Change From Baseline to Week 12 in Waist Circumference | -1.5 cm | Standard Deviation 3 |
p-value: <0.001t-test, 2 sided
Secondary
Oral Glucose Tolerance Testing - Change From Baseline to Week 12 in 120 Minute Glucose
Oral glucose testing
Time frame: baseline to 12 weeks
Population: The analysis population reported here comprised the subjects who received at least one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Serostim | Oral Glucose Tolerance Testing - Change From Baseline to Week 12 in 120 Minute Glucose | 11.7 mg/dL | Standard Deviation 43.7 |
p-value: 0.007t-test, 2 sided
Secondary
Oral Glucose Tolerance Testing - Change From Baseline to Week 12 in Fasting Glucose
Oral glucose testing
Time frame: baseline to 12 weeks
Population: The analysis population reported here comprised the subjects who received at least one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Serostim | Oral Glucose Tolerance Testing - Change From Baseline to Week 12 in Fasting Glucose | 4.5 mg/dL | Standard Deviation 20.4 |
p-value: 0.015t-test, 2 sided
Secondary
Oral Glucose Tolerance Testing - Change From Baseline to Week 12 in Fasting Insulin
Oral glucose tolerance testing
Time frame: baseline to 12 weeks
Population: The analysis population reported here comprised the subjects who received at least one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Serostim | Oral Glucose Tolerance Testing - Change From Baseline to Week 12 in Fasting Insulin | 10.8 mcIU/mL | Standard Deviation 22.3 |
p-value: <0.001t-test, 2 sided