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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00119769
• Other study ID #: KFE001
• Status: Completed
• Phase: Phase 4
• First received: July 7, 2005
• Last updated: August 26, 2008
• Start date: February 2005
• Est. completion date: July 2008

Study information

• Verified date: August 2008
• Source: Hvidovre University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines AgencyDenmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: July 2008
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 21 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Lipodystrophy

Intervention

Drug:
• Placebo
Placebo, 0.7 mg/day injected subcutaneously
• Genotropin (human recombinant Growth hormone)
Genotropin, 0.7 mg/day injected subcutaneously

Locations

Country	Name	City	State
Denmark	Clinical Research Unit, Hvidovre University Hospital	Hvidovre

Sponsors (2)

Lead Sponsor	Collaborator
Hvidovre University Hospital	Pfizer

Country where clinical trial is conducted

Denmark, 

References & Publications (6)

Andersen O, Haugaard SB, Flyvbjerg A, Andersen UB, Ørskov 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. — View 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. — View 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. — View Citation

Haugaard SB, Andersen O, Hansen BR, Andersen UB, Vølund 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. — View 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. — View Citation

Haugaard SB, Andersen O, Vølund 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. Erratum in: Clin Endocrinol (Oxf). 2006 Oct;65(4):554. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Impact of hGH 0.7 mg/day on number of mature and naïve CD4 cells in HIV patients at 9 months		9 months	No
Secondary	Impact of hGH 0.7 mg/day at 9 months on thymic size		9 months	No
Secondary	Impact of hGH 0.7 mg/day at 9 months on fat distribution as measured with CT and DEXA scans		9 months	No
Secondary	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	Yes
Secondary	Impact of hGH 0.7 mg/day at 9 months on insulin sensitivity as measured by hyperinsulinaemic euglycaemic clamp		9 months	Yes
Secondary	Impact of hGH 0.7 mg/day at 9 months on lipid profile		9 months	No
Secondary	Impact of hGH 0.7 mg/day at 9 months on quality of life and adherence to HAART		9 months	No
Secondary	Impact of hGH 0.7 mg/day at 9 months on cytokines		9 months	No
Secondary	Impact of hGH 0.7 mg/day at 9 months on safety parameters		9 months	Yes