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

NCT ID: NCT00119769

Last Updated: 2008-08-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-02-28
• Study Completion Date: 2008-07-31

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.

Conditions

HIV Infections; Lipodystrophy

Keywords

HIV; immune stimulation; lipodystrophy; growth hormone; recombinant growth hormone; Treatment Experienced

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo, 0.7 mg/day injected subcutaneously

2

Group Type: ACTIVE_COMPARATOR

Genotropin (human recombinant Growth hormone)

Intervention Type: DRUG

Genotropin, 0.7 mg/day injected subcutaneously

Interventions

Placebo

Placebo, 0.7 mg/day injected subcutaneously

Intervention Type: DRUG

Genotropin (human recombinant Growth hormone)

Genotropin, 0.7 mg/day injected subcutaneously

Intervention Type: DRUG

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Hvidovre University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Clinical Research Center, Copenhagen University Hospital Hvidovre, Denmark

Principal Investigators

Birgitte R Hansen, MD

Role: PRINCIPAL_INVESTIGATOR

Locations

Clinical Research Unit, Hvidovre University Hospital

Hvidovre, , Denmark

Countries

Denmark

References

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.

Reference Type: BACKGROUND

PMID: 15764170 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15762193 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15730419 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15690310 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15562401 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15305891 (View on PubMed)

Other Identifiers

KFE001

Identifier Type: -

Identifier Source: org_study_id