The Effect of Low-Dose Human Growth Hormone Therapy in HIV Infected Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effect of Low-Dose Human Growth Hormone Therapy in HIV Infected Patients on Highly Active Antiretroviral Therapy (HAART)

Conditions
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HIV Infections, Lipodystrophy

Intervention / Treatment
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* Drug: Placebo
* Drug: Genotropin (human recombinant Growth hormone)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: Placebo<br>* Placebo, 0.7 mg/day injected subcutaneously<br>|
| Active Comparator: 2<br> | Drug: Genotropin (human recombinant Growth hormone)<br>* Genotropin, 0.7 mg/day injected subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of hGH 0.7 mg/day on number of mature and naïve CD4 cells in HIV patients at 9 months |  | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of hGH 0.7 mg/day at 9 months on thymic size |  | 9 months | 
| Impact of hGH 0.7 mg/day at 9 months on fat distribution as measured with CT and DEXA scans |  | 9 months | 
| 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 |  | 9 months | 
| Impact of hGH 0.7 mg/day at 9 months on insulin sensitivity as measured by hyperinsulinaemic euglycaemic clamp |  | 9 months | 
| Impact of hGH 0.7 mg/day at 9 months on lipid profile |  | 9 months | 
| Impact of hGH 0.7 mg/day at 9 months on quality of life and adherence to HAART |  | 9 months | 
| Impact of hGH 0.7 mg/day at 9 months on cytokines |  | 9 months | 
| Impact of hGH 0.7 mg/day at 9 months on safety parameters |  | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, immune stimulation, lipodystrophy, growth hormone, recombinant growth hormone, Treatment Experienced