Body Weight Changes, HIV-Associated Lipodystrophy Syndrome, HIV Infections, Insulin Resistance, Metabolic Syndrome X
Conditions
Keywords
Lipodystrophy, HIV, Growth hormone, Rosiglitazone, Visceral fat, Metabolic syndrome, Treatment Experienced, Visceral fat accumulation, fat accumulation, HIV-Associated Metabolic Syndrome
Brief summary
The purpose of the study is to determine if the combination of recombinant human growth hormone plus rosiglitazone (an insulin-sensitizing drug) is safe and more effective than either drug alone (or no active therapy) for the treatment of fat accumulation in people with HIV infection and insulin resistance.
Detailed description
A number of people with HIV infection who gain weight in the abdomen (sometimes called lipodystrophy) also have a high level of the sugar-controlling hormone called insulin. These people need to produce this extra insulin to help keep their blood sugar normal. This is called insulin resistance. Studies have shown that growth hormone (also called Serostim) can decrease abdominal fat, but it can also worsen the insulin resistance. Rosiglitazone (also called Avandia) is used to treat insulin resistance in people who have diabetes, so we want to see if taking growth hormone and rosiglitazone together will be better for treating the fat accumulation part of lipodystrophy than either drug alone or no active therapy. The study is 24 weeks long, divided into two 12-week parts. The first part of the study is double-blind, meaning that neither participants nor the study staff will know which drugs participants are on. Participants will be assigned randomly (like flipping a coin) to one of four groups: 1. Growth hormone (one injection, daily) PLUS rosiglitazone (one tablet, twice daily). 2. Growth hormone PLUS rosiglitazone placebo (sugar pill). 3. Growth hormone placebo (plain water injection) PLUS rosiglitazone. 4. Growth hormone placebo PLUS rosiglitazone placebo. Everyone in the study will need to be hospitalized overnight for special tests at the beginning of the study and at week 12. The second part of the study is open-label, meaning that participants and the study staff will know which drugs participants are receiving. All volunteers will receive both active drugs: * Growth hormone (one 2 mg injection, every other day) PLUS rosiglitazone (one 4 mg tablet, twice daily).
Interventions
DRUGRosiglitazone
4 mg tablet twice a day x 12 weeks (double-blind phase)
DRUGRecombinant human growth hormone + rosiglitazone
Recombinant human growth hormone or placebo 3 mg s.c. x 12 weeks (double-blind phase)
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* HIV-infected * On stable Food and Drug Administration (FDA)-approved antiretrovirals for at least 8 weeks * Excess abdominal fat based on waist and hip measurements done at the screening visit. \[waist greater than 34.7 inches (men) or 29.6 inches (women) and waist to hip ratio greater than 0.95 (men) or 0.9 (women)\] * Evidence of insulin resistance (based on fasting glucose and insulin levels done at screening) * Triglycerides less than 750 mg/dL
Exclusion criteria
* Pregnancy * Active AIDS-defining infection or other acute illness, within 30 days of entry. * Active cancer (except for localized Kaposi's sarcoma) or active brain tumor * Any diagnosis of pancreatitis, carpal tunnel syndrome, diabetes, angina, coronary artery disease, or disorder associated with fluid retention (examples: cirrhosis, congestive heart failure) * Untreated or uncontrolled high blood pressure, within 30 days of entry. * Within 12 weeks of study entry, use of the following: * Obesity (fat-reducing) drugs. * Anti-diabetic or insulin-sensitizing drugs (examples: rosiglitazone, pioglitazone, or metformin). * Systemic glucocorticoids (example: prednisone). * Growth hormone or any medication for AIDS-associated wasting. * Systemic chemotherapy, interferon, or radiation therapy. * Androgenic agents \[examples: nandrolone, oxandrolone (Oxandrin) (testosterone replacement therapy is permitted if started more than 30 days before entry)\] * Appetite stimulants (Marinol, Megace, Periactin). * Use of cholesterol lowering drugs, unless started more than 12 weeks before entry * Inability to have a magnetic resonance imaging (MRI) scan performed (examples: cardiac pacemaker, intracranial aneurysm clips)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Insulin Sensitivity | 12 weeks | Change in insulin sensitivity value from baseline to week 12 by frequently sampled intravenous glucose tolerance test This assessment was only conducted at baseline and week 12; therefore the change reflects the difference between these two time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visceral Adipose Tissue Volume | 12 weeks | Change in visceral adipose tissue volume from baseline to week 12 measured by whole body MRI Data are presented only for subjects who had MRI scans done at both time points. |
| Change in Subcutaneous Adipose Tissue Volume | 12 weeks | Change in subcutaneous adipose tissue volume from baseline to week 12 by whole body MRI Data are presented only for subjects who had MRI scans done at both time points. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rhGH + Rosi Recombinant human growth hormone + rosiglitazone
Rosiglitazone: 4 mg tablet twice a day x 12 weeks (double-blind phase)
Recombinant human growth hormone + rosiglitazone: Recombinant human growth hormone or placebo 3 mg s.c. x 12 weeks (double-blind phase) | 22 |
| rhGH Placebo + Rosi Placebo for recombinant human growth hormone + rosiglitazone
Rosiglitazone: 4 mg tablet twice a day x 12 weeks (double-blind phase)
Recombinant human growth hormone + rosiglitazone: Recombinant human growth hormone or placebo 3 mg s.c. x 12 weeks (double-blind phase) | 19 |
| rhGH + Rosi Placebo Recombinant human growth hormone + placebo for rosiglitazone
Rosiglitazone: 4 mg tablet twice a day x 12 weeks (double-blind phase)
Recombinant human growth hormone + rosiglitazone: Recombinant human growth hormone or placebo 3 mg s.c. x 12 weeks (double-blind phase) | 17 |
| Double Placebo Placebo for recombinant human growth hormone + placebo for rosiglitazone
Rosiglitazone: 4 mg tablet twice a day x 12 weeks (double-blind phase)
Recombinant human growth hormone + rosiglitazone: Recombinant human growth hormone or placebo 3 mg s.c. x 12 weeks (double-blind phase) | 19 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 | 0 |
| Overall Study | Missing lab specimens | 0 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | Total | rhGH + Rosi | rhGH Placebo + Rosi | rhGH + Rosi Placebo | Double Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 47.9 years STANDARD_DEVIATION 7.1 | 46.8 years STANDARD_DEVIATION 9.4 | 49.3 years STANDARD_DEVIATION 6.1 | 48.6 years STANDARD_DEVIATION 4.9 | 46.6 years STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 30 Participants | 9 Participants | 9 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 13 Participants | 10 Participants | 14 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 49 Participants | 15 Participants | 11 Participants | 11 Participants | 12 Participants |
| Sex: Female, Male Female | 17 Participants | 4 Participants | 4 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 60 Participants | 18 Participants | 15 Participants | 14 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 22 | 11 / 18 | 14 / 15 | 9 / 17 |
| serious Total, serious adverse events | 1 / 22 | 1 / 19 | 0 / 17 | 3 / 19 |
Outcome results
Primary
Change in Insulin Sensitivity
Change in insulin sensitivity value from baseline to week 12 by frequently sampled intravenous glucose tolerance test This assessment was only conducted at baseline and week 12; therefore the change reflects the difference between these two time points.
Time frame: 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| rhGH + Rosi | Change in Insulin Sensitivity | 0.20 uU*10^-4*min*ml^-1 |
| rhGH Placebo + Rosi | Change in Insulin Sensitivity | 1.44 uU*10^-4*min*ml^-1 |
| rhGH + Rosi Placebo | Change in Insulin Sensitivity | -0.63 uU*10^-4*min*ml^-1 |
| Double Placebo | Change in Insulin Sensitivity | 0.14 uU*10^-4*min*ml^-1 |
Secondary
Change in Subcutaneous Adipose Tissue Volume
Change in subcutaneous adipose tissue volume from baseline to week 12 by whole body MRI Data are presented only for subjects who had MRI scans done at both time points.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhGH + Rosi | Change in Subcutaneous Adipose Tissue Volume | -0.11 L | Standard Deviation 3.33 |
| rhGH Placebo + Rosi | Change in Subcutaneous Adipose Tissue Volume | 0.74 L | Standard Deviation 1.86 |
| rhGH + Rosi Placebo | Change in Subcutaneous Adipose Tissue Volume | -0.38 L | Standard Deviation 1.23 |
| Double Placebo | Change in Subcutaneous Adipose Tissue Volume | -0.03 L | Standard Deviation 2.64 |
Secondary
Change in Visceral Adipose Tissue Volume
Change in visceral adipose tissue volume from baseline to week 12 measured by whole body MRI Data are presented only for subjects who had MRI scans done at both time points.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhGH + Rosi | Change in Visceral Adipose Tissue Volume | -1.13 L | Standard Deviation 1.41 |
| rhGH Placebo + Rosi | Change in Visceral Adipose Tissue Volume | -0.19 L | Standard Deviation 0.69 |
| rhGH + Rosi Placebo | Change in Visceral Adipose Tissue Volume | -1.15 L | Standard Deviation 0.81 |
| Double Placebo | Change in Visceral Adipose Tissue Volume | -0.04 L | Standard Deviation 0.9 |