Trial record 9 of 31 for:    " November 11, 2009":" December 11, 2009"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Effect of HIV Infection and Highly Active Antiretroviral Treatment (HAART) on Bone Homeostasis (OPG-2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Emory University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Ighovwerha Ofotokun, Emory University
ClinicalTrials.gov Identifier:
NCT01020045
First received: November 24, 2009
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

Advances in HAART have been a huge success story in the management of HIV infection. However, serious metabolic complications including osteoporosis and bone fractures are increasingly been seen with HAART, and the responsible mechanisms remain poorly elucidated.

The skeleton continually regenerates through homeostatic bone remodeling. Osteoclasts the cells responsible for bone resorption form under the influence of the key osteoclastogenic cytokine Receptor- Activator of NF-KB (RANKL). The osteoclastogenic and pro-resorptive activities of RANKL are moderated by its physiological decoy receptor osteoprotegerin (OPG). Increase in the ratio of RANKL to OPG accelerates the rate of osteoclastic bone resorption leading to osteoporosis.

The investigators' preliminary studies have now demonstrated that in an animal model of HIV/AIDS, the HIV-1 Transgenic rat, the development of osteoporosis is recapitulated as observed in human patients. Furthermore, the investigators found that B cell expression of OPG is significantly downregulated, concurrent with a significant upregulation in production of RANKL.


Condition
HIV Infection
Osteopenia
Osteoporosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Effect of HIV Infection and HAART on Bone Homeostasis

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • To correlate serum and B cell and T cell OPG and/or RANKL production in treatment-naïve HIV-infected patients, with indices of bone turnover and structure and with viral load. [ Time Frame: During entry visit ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: October 2010
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
HIV-seropositive, HIV seronegative
No intervention - biologic samples were collected from both HIV positive and HIV negative subjects
Treatment naive subjects
HIV-seropositive subjects naive to antiretroviral therapy. HIV-seronegative subjects otherwise healthy.

Detailed Description:

The investigators hypothesize that "immunological disruption of B cell number and/or function, may play a key causal role in the bone loss associated with HIV/AIDS, by driving a "switch" from OPG production to overproduction of RANKL". The investigators propose to determine the role of perturbations in B and T cells on OPG and RANKL production and on bone turnover.

This is a cross-sectional analysis of changes in BMD (DXA), and B cell and T cell function in HIV seronegative/seropositive subjects matched by known risk factors for osteoporosis. Serum will be collected for quantitation of total OPG and RANKL, and for biochemical markers of bone turnover (CTx, and TRAP5b), specific and sensitive markers of osteoclast activity, and for osteocalcin and P1NP, specific and sensitive markers of bone formation by commercial ELISAs. Peripheral blood mononuclear cells (PBMC) will be isolated and total and percentage frequency and absolute number (/mL) of B cells (CD19+) and T cells (CD3) and their subsets (CD4 and CD8). B cells (CD19) and T cells (CD3 and CD4 and CD8) will be immunomagnetically purified and OPG and RANKL mRNA and protein production quantitated by RT-PCR and ELISA respectively. As a secondary endpoint, B cells will be fractionated into subsets based on differential expression of the markers CD10, CD21 and CD27 and OPG and RANKL production quantitated by in each subset by intracellular staining and FACS analysis.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Healthy (HIV sero-negative) volunteers and otherwise healthy antiretroviral treatment naïve HIV-1 sero-positive patients, age >18 years.

Criteria

Inclusion Criteria:

  1. Healthy (sero-negative) volunteers and otherwise healthy treatment naïve HIV-1 sero-positive patient.
  2. Age >30<50 years and segregated into age and gender ranges as described above in section 3.2 (15 subjects per stratification based on Power Test).
  3. Ability and willingness of subject or legal guardian/representative to give written informed consent.
  4. Antiretroviral naivety.
  5. No CD4 T-cell counts requirement.
  6. Absence of non-HIV related active immunological or bone disorders such as;

    • Bone marrow or organ transplantation
    • Inflammatory bowel disease (ulcerative colitis, crohn's disease)
    • Multiple Myeloma
    • Osteogenesis imperfect
    • Osteomalacia
    • Osteosarcoma
    • Paget's disease
    • Postmenopausal osteoporosis
    • Rheumatoid arthritis
    • Systemic lupus erythematosus
  7. Laboratory values obtained within 90 days prior to study entry:

    • Hemoglobin >9.4 g/dl
    • Creatinine < 2 mg/dl
    • AST (SGOT) < 2 x ULN
    • ALT (SGPT) < 2 x ULN

Exclusion Criteria:

  1. Physical or biochemical evidence or a medical history of malignancy.
  2. Currently (within the past 8 weeks) taking any medication with known influence on the immune or skeletal system (e.g. immune modulation therapy, glucocorticoids, steroid hormones, bisphosphonates).
  3. The patient is not fully ambulatory.
  4. Pregnancy or breast feeding.

Exclusion criteria are primarily centered on immunological aspects with bone related aspects secondary. This is because in our model immunological function is proximal to bone function. Consequently, use of vitamin D or calcium supplementation will not be exclusion criteria, but will be added as covariates in our analysis.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01020045

Contacts
Contact: Ighovwerha Ofotokun, MD, MSc 404-616-0659 iofotok@emory.edu
Contact: Mervyn N Weitzmann, PhD 404-727-1389 mweitzm@emory.edu

Locations
United States, Georgia
Grady Infectious Diseases Program Clinic Recruiting
Atlanta, Georgia, United States, 30308
Contact: Ighovwerha Ofotokun, MD, MSc    404-616-0659    iofotok@emory.edu   
Sub-Investigator: Melvin N Weitzmann, PhD         
Sub-Investigator: Jeffrey L Lennox, MD         
Sub-Investigator: Carlos del Rio, MD         
Sub-Investigator: Wendy Armstrong, MD         
Sub-Investigator: Molly Eaton, MD         
Sub-Investigator: Clifford Gunthel, MD         
Sub-Investigator: Melody Palmore, MD         
Sub-Investigator: Kirk A Easley, MS         
Sub-Investigator: Anandi Sheth, MD         
Grady Infectious Diseases Program Clinic Recruiting
Atlanta, Georgia, United States, 30308
Contact: Ighovwerha Ofotokun, MD, MSc    404-616-0659    iofotok@emory.edu   
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Ighovwerha Ofotokun, MD, MSc Emory University
  More Information

No publications provided

Responsible Party: Ighovwerha Ofotokun, Associate Professor of Medicine, Emory University
ClinicalTrials.gov Identifier: NCT01020045     History of Changes
Other Study ID Numbers: IRB00027210, R01AR059364-01
Study First Received: November 24, 2009
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
HIV
Osteopenia
Osteoporosis

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Bone Diseases, Metabolic
Osteoporosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Bone Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on September 11, 2014