Clinical trial NCT00119769: The Effect of Low-Dose Human Growth Hormone Therapy in HIV Infected Patients
Official title: The Effect of Low-Dose Human Growth Hormone Therapy in HIV Infected Patients on Highly Active Antiretroviral Therapy (HAART)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Lipodystrophy
Keywords: HIV
immune stimulation
lipodystrophy
growth hormone
recombinant growth hormone
Treatment Experienced
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2005-07-14
Enrollment: 46
Sex: MALE
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the effect of low-dose human growth hormone therapy on immune status and fat morphology.

Detailed description: Following the introduction of highly active antiretroviral therapy (HAART) in the mid-nineties, the improvement in the clinical course of HIV has lead to a dramatic reduction in morbidity and mortality. However, a growing concern has been the emergence of an increasing number of drug therapy failure, mainly caused by rebounding virus. This effect in turn is prompted respectively by developing resistance and failing compliance mainly due to early or late adverse reactions. These adverse reactions mainly consists of a number of metabolic and morphologic changes, known as HIV associated lipodystrophy syndrome (HALS) and affects approximately 40 % of HIV infected patients on HAART. HALS is characterized by lipoatrophy on extremities, gluteal and facial regions combined with intraabdominal lipoaccumulation, "buffalo hump" and lipomas.

Thus, despite progress in the development of new drugs with new targets and resistance profiles the need for agents with immune modulating properties is evident, both as a way to overcome the problems of resistance and hopefully modify treatment regimens in order to reduce the exposure to late adverse reactions caused by HAART. A number of studies have addressed the problems of modulating the immune response during HIV infection. Results are promising but a major obstacle seems to be adverse effects. In the pre-HAART era high dose human growth hormone (hGH) therapy has been used for HIV wasting and in the HAART era the impact on fat distribution in HIV infected patients have been investigated based on the lipolytic properties of hGH. However high dosage of hGH has been associated with severe adverse effects limiting the usefulness in daily clinical practice. One recent study demonstrated increments in thymic mass and a rise in the number of circulating naïve CD4 T cells upon treatment with high dose hGH. Our group has conducted a 60 week pilot study with daily injection of 0.7 mg genotropin, demonstrating an immune stimulating effect as well as an increased limb fat/truncal fat ratio, without metabolic and clinically recognizable side effects. Based on these findings we plan to perform a randomized, double blind, prospective, interventional study including 50 HIV infected patients on HAART, investigating the effect of low dose hGH on immune status and fat distribution.

Eligibility criteria: Inclusion Criteria:

* Male
* Caucasian race
* Age \>21 years, \<60 years
* HIV-1 infection
* HAART treated \> 12 months
* HIV-RNA \< 100 copies/ml
* CD4 count \> 200
* Fasting plasma glucose \< 6.1 mM
* Stable weight

Exclusion Criteria:

* BMI \> 28 kg/m2 and BMI \< 18.5 kg/m2
* Wasting or AIDS defining disease
* Severe chronic diseases other than HIV
* Cancer, previous transplantation
* Previous AMI
* Diabetes
* Hormonal substitution therapy
* Lipid lowering or antidiabetic therapy within 3 months
* Abuse of narcotics or alcohol
* Major psychiatric disorders
* Adverse reactions towards Genotropin
* Calcium-ion \< 1.15 or \> 1.35 mM
* D-vitamin \< 19 nM
* TSH \< 0.1 or \> 10 mIU/l

Primary outcomes:
measure: Impact of hGH 0.7 mg/day on number of mature and naïve CD4 cells in HIV patients at 9 months
timeFrame: 9 months
Secondary outcomes:
measure: Impact of hGH 0.7 mg/day at 9 months on thymic size
timeFrame: 9 months
measure: Impact of hGH 0.7 mg/day at 9 months on fat distribution as measured with CT and DEXA scans
timeFrame: 9 months
measure: Impact of hGH 0.7 mg/day at 9 months on glucose metabolism i.e.glucose tolerance, insulin sensitivity and beta cell function as measured by OGTT
timeFrame: 9 months
measure: Impact of hGH 0.7 mg/day at 9 months on insulin sensitivity as measured by hyperinsulinaemic euglycaemic clamp
timeFrame: 9 months
measure: Impact of hGH 0.7 mg/day at 9 months on lipid profile
timeFrame: 9 months
measure: Impact of hGH 0.7 mg/day at 9 months on quality of life and adherence to HAART
timeFrame: 9 months
measure: Impact of hGH 0.7 mg/day at 9 months on cytokines
timeFrame: 9 months
measure: Impact of hGH 0.7 mg/day at 9 months on safety parameters
timeFrame: 9 months
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Clinical Research Unit, Hvidovre University Hospital
Study officials:
name: Birgitte R Hansen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andersen O, Haugaard SB, Hansen BR, Orskov H, Andersen UB, Madsbad S, Iversen J, Flyvbjerg A. Different growth hormone sensitivity of target tissues and growth hormone response to glucose in HIV-infected patients with and without lipodystrophy. Scand J Infect Dis. 2004;36(11-12):832-9. doi: 10.1080/00365540410021162.
citation: Haugaard SB, Andersen O, Dela F, Holst JJ, Storgaard H, Fenger M, Iversen J, Madsbad S. Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic beta-cells. Eur J Endocrinol. 2005 Jan;152(1):103-12. doi: 10.1530/eje.1.01835.
citation: Haugaard SB, Andersen O, Volund A, Hansen BR, Iversen J, Andersen UB, Nielsen JO, Madsbad S. Beta-cell dysfunction and low insulin clearance in insulin-resistant human immunodeficiency virus (HIV)-infected patients with lipodystrophy. Clin Endocrinol (Oxf). 2005 Mar;62(3):354-61. doi: 10.1111/j.1365-2265.2005.02223.x.
citation: Haugaard SB, Andersen O, Hansen BR, Andersen UB, Volund A, Iversen J, Nielsen JO, Madsbad S. In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance. Metabolism. 2005 Feb;54(2):171-9. doi: 10.1016/j.metabol.2004.08.009.
citation: Haugaard SB, Andersen O, Hansen BR, Orskov H, Andersen UB, Madsbad S, Iversen J, Flyvbjerg A. Insulin-like growth factors, insulin-like growth factor-binding proteins, insulin-like growth factor-binding protein-3 protease, and growth hormone-binding protein in lipodystrophic human immunodeficiency virus-infected patients. Metabolism. 2004 Dec;53(12):1565-73. doi: 10.1016/j.metabol.2004.06.025.
citation: Andersen O, Haugaard SB, Flyvbjerg A, Andersen UB, Orskov H, Madsbad S, Nielsen JO, Iversen J. Low-dose growth hormone and human immunodeficiency virus-associated lipodystrophy syndrome: a pilot study. Eur J Clin Invest. 2004 Aug;34(8):561-8. doi: 10.1111/j.1365-2362.2004.01380.x.