Trial registered on ANZCTR


Trial ID
ACTRN12615001258549
Ethics application status
Approved
Date submitted
14/10/2015
Date registered
17/11/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of moderate physical activity (briskwalking) on metabolic and inflammatory markers in people living with HIV
Scientific title
Effects of moderate physical activity on metabolic and inflammatory markers in HIV infected patients treated with combination antiretroviral therapy
Secondary ID [1] 287642 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV infection 296464 0
Inflammation 296465 0
Physical inactivity 296466 0
Metabolic problems 296503 0
Condition category
Condition code
Inflammatory and Immune System 296722 296722 0 0
Other inflammatory or immune system disorders
Infection 296723 296723 0 0
Acquired immune deficiency syndrome (AIDS / HIV)
Physical Medicine / Rehabilitation 296724 296724 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Moderate physical activity: groups of 10-15 subjects trained three times a week for 12 weeks in the periods March-July, 2011 and 2012.

1) Training group 1: 60 minutes of brisk walking at an intensity of 65-75% of maximal heart rate.

2) Training group 2: 30 minutes of circuit training: crunch, lat machine, chest press, leg press, leg extension, sitting calf. Each exercise was repeated 12 times for three sets at 65% of 1-Repetition Maximum Test After that 60 minutes of brisk walking at an intensity of 65-75% of maximal heart rate was performed (Total training time 90 minutes).

Professional coaches followed all the training sessions providing technical instruction, supervision and encouragement. Participants received generic dietary advice. Adherence was measured by frequency of attended training sessions.
Intervention code [1] 293040 0
Lifestyle
Intervention code [2] 293060 0
Treatment: Other
Comparator / control treatment
Training group 1: comparator

Training group 2: intervention group
Control group
Active

Outcomes
Primary outcome [1] 296343 0
Composite primary outcome: variation of metabolic markers including those defining the metabolic syndrome.

Triglycerides, HDL cholesterol and fasting glucose were collected at baseline and after 12 weeks of training; fasting blood samples were collected and processed locally according to standardized protocols.
Timepoint [1] 296343 0
Baseline and after 12 weeks of training
Primary outcome [2] 296583 0
Waist Circumference was measured at baseline and after 12 weeks of training with a tape at the mid-point between the last costal arch and the iliac crest.
Timepoint [2] 296583 0
Baseline and after 12 weeks of training
Primary outcome [3] 296584 0
Blood pressure was measured at baseline and after 12 weeks of training with a sphygmomanometer.
Timepoint [3] 296584 0
Baseline and after 12 weeks of training
Secondary outcome [1] 318215 0
Variation of mental well-being: Medical Outcomes Trust Short-Form 36-item version
Timepoint [1] 318215 0
After 12 weeks of training
Secondary outcome [2] 318216 0
Variation of autonomic control

After an initial period of resting of 20 min in supine position, beat-by-beat series of R-R intervals were measured in supine position for 10 min and then in orthostatic position for other 10 min, by a HR monitor (S810, Polar Electro Oy, Finland), validated for HRV analysis
Timepoint [2] 318216 0
After 12 weeks of training
Secondary outcome [3] 318217 0
Variation of bone metabolism

Bone mineral density, t-score and z-score in spine and femoral, trochanter and ward iwas measured by dual-energy X-ray absorptiometry (DEXA) (Lunar Prodigy, version 8.8, GE Medical Systems, Madison, WI).
Timepoint [3] 318217 0
After 12 weeks of training
Secondary outcome [4] 318280 0
Variation of body composition

Anthropometric variables included weight, body mass index (BMI), waist, hip, and thigh circumference on dominant side.

Total and % fat mass, lean mass and body mineral content (BMC) at arms, limbs, trunk and as total body was measured by dual-energy X-ray absorptiometry (DEXA) (Lunar Prodigy, version 8.8, GE Medical Systems, Madison, WI).

Superficial and visceral fat was measured by ultrasonography at the periumbilical skin-point.
Timepoint [4] 318280 0
After 12 weeks of training
Secondary outcome [5] 318281 0
Variation of inflammatory markers

Soluble markers. Soluble biomarkers were measured in cryopreserved plasma samples, drawn at baseline and after 12 weeks of training, by commercially available enzyme-linked immunosorbent assays according to manufacturers’ recommendation. These included high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and soluble CD14 (sCD14)(R&D Systems, Minneapolis, MN), D-dimer (Asserachrom, Diagnostica Stago, Asnieres-Sur-Seine, France), interleukin-18 (IL-18)(Medical and Biological Laboratories, Nagoya, Japan) and myostatin (Cusabio Biotech, Wuhan, China).

Flow cytometry for cell-activation markers. T-cell activation was measured on cryopreserved peripheral blood mononuclear cells isolated by Ficoll-Paque gradient from EDTA-anticoagulated whole blood. After thawing and PBS-washing, 3 x 105 cells were stained using phycoerythrin (PE)-conjugated anti-HLA-DR, PE-cyanin red 5.1-conjugated anti-CD38, Alexa Fluor 647-conjugated anti-CD3, fluorescein isothiocyanate-conjugated anti-CD4 or anti-CD8 (BD-Biosciences, San Diego, CA). CD38+ and HLA-DR+ cells were gated from the CD3+/CD4+ or CD3+/CD8+ cells on a 2-dimensional dot plot. Analyses were performed by FACSCalibur with CellQuest software (BD-Biosciences) and results reported as percentages of CD3+/CD4+ and CD3+/CD8+ T-cells expressing both HLA-DR and CD38.
Timepoint [5] 318281 0
After 12 weeks of training
Secondary outcome [6] 318282 0
Variation of physical fitness

6 Minutes Walking Test (6MWT). Participants were instructed to walk as fast as possible for six minutes on a 400 m outdoor athletic track. HRmean was recorded during the test, blood lactate concentration was assessed before and 3 minutes after 6MWT (Lactate ProTM, Arkray KdK, Japan), and the Rating of Perceived Exertion (RPE) before and at the end of 6MWT.

Strength measurements. 1-RM test assessed the maximal load lifted in one repetition, and the 30-seconds crunch test the number of crunches performed in 30 seconds.
Timepoint [6] 318282 0
After 12 weeks of training
Secondary outcome [7] 318283 0
Variation of additional metabolic markers

Blood examination included complete blood count; standard biochemical exams with fasting total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, insulin, HbA1c; CD4+ and CD8+ T-cell counts, HIV-1-RNA plasma level (Abbott RealTime HIV-1 assay). The Homeostatic Model Assessment (HOMA)-I and the Veterans Aging Cohort Study Risk (VACS) indexes were calculated
Timepoint [7] 318283 0
After 12 weeks of training

Eligibility
Key inclusion criteria
Age: between 18 and 75 years of age;
HIV infection
cART: greater than 6 months;
Sedentary lifestyle: defined as physical activity for <2 days per week for <20 minutes per session;
Either evidence of lipodystrophy or of at least one of the Adult Treatment Panel III definition criteria of the metabolic syndrome
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any disease requiring hospitalization in the 6 weeks before enrolment; medical conditions contraindicating exercise as established by a sport medicine specialist; inability to walk at brisk pace; current substance or alcohol abuse.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)

Recruitment
Recruitment status
Completed
Anticipated date of first participant enrolment
Actual date of first participant enrolment
4/03/2011
Anticipated date last participant enrolled
Actual date last participant enrolled
20/02/2012
Anticipated date of last data collection
Actual date of last data collection
Target sample size
60
Actual sample size
49
Recruitment outside Australia
Country [1] 7218 0
Italy
State/province [1] 7218 0
Milano

Funding & Sponsors
Funding source category [1] 292228 0
Charities/Societies/Foundations
Name [1] 292228 0
Associazione Solidarieta AIDS (ASA) onlus
Address [1] 292228 0
Via Arena, 25, 20142 Milano
Country [1] 292228 0
Italy
Funding source category [2] 292229 0
Charities/Societies/Foundations
Name [2] 292229 0
ANLAIDS onlus
Address [2] 292229 0
via Giovanni Giolitti, 42 00185 Roma
Country [2] 292229 0
Italy
Primary sponsor type
Hospital
Name
San Raffaele Scientific Institute
Address
Via Olgettina, 60
20132 Milano
Country
Italy
Secondary sponsor category [1] 290902 0
University
Name [1] 290902 0
Universita degli Studi di Milano
Address [1] 290902 0
Via Festa del Perdono, 7
20122 Milano
Country [1] 290902 0
Italy

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293677 0
San Raffaele Scientific Institute
Ethics committee address [1] 293677 0
Ethics committee country [1] 293677 0
Italy
Date submitted for ethics approval [1] 293677 0
Approval date [1] 293677 0
03/03/2011
Ethics approval number [1] 293677 0

Summary
Brief summary
The use of antiretroviral drugs has dramatically reduced the progression and mortality of HIV infection, which has now become a chronic condition. However, this treatment involves taking several medications, which must be used in combination for the entire life. Side effects are frequent and occur with alterations of cardiovascular system, renal system, bone mineralisation. In addition, chronic HIV infection is per se associated with increased systemic immune activation. As a result there is an increased risk in HIV-infected patients to develop cardiovascular and cerebrovascular diseases, diabetes, renal failure, osteoporosis and other problems resulting from metabolic disorders.

There are several measures that can be implemented to reduce the risk of developing these conditions, which include both interventions of lifestyle, such as diet and exercise, and different pharmacological approaches. Among these interventions, there are several evidences that physical activity is helpful in reducing the risk of cardiovascular diseases in the general population, changing the risk factors for these diseases. There are preliminary evidences that physical exercise is also effective in HIV-positive people with impaired metabolism in modifying several risk factors for developing cardiovascular disease.

The effects of physical activity are different depending on the type and intensity of physical activity. Generally, aerobic exercise improves cardiovascular parameters, while resistance training counteracts the reduction of muscle mass. In people while type 2 diabetes, the combination of the two types of activity improves cardiovascular and metabolic parameters. Aerobic exercise seems effective in reducing body fat in HIV-infected people with increased storage of fat in the abdomen, while the combination of aerobic and resistance training seems to be effective in reducing abdominal fat, total fat, total cholesterol, LDL-cholesterol and triglycerides.

The study aims to evaluate the benefits of moderate physical activity for people living with HIV infection treated with antiretroviral drugs, including aerobic physical activity or the combination of aerobic and resistance training. Benefits will be measured by an improvement of the state of health, physical fitness, and metabolic and inflammatory markers, and it also intends to assess whether the combination of aerobic and resistance training is superior to aerobic activity only. The innovative aspect of this program in the inclusion, as aerobic activity, of brisk walking, that is a technique for walking a high speed engaging significantly the muscular and cardiovascular system.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60922 0
Dr Paola Cinque
Address 60922 0
Department of Infectious Diseases
San Raffaele Hospital
Va Stamira d'Ancona
20127 Milano
Country 60922 0
Italy
Phone 60922 0
+39 0226433160
Fax 60922 0
Email 60922 0
cinque.paola@hsr.it
Contact person for public queries
Name 60923 0
Dr Paola Cinque
Address 60923 0
Department of Infectious Diseases
San Raffaele Hospital
Va Stamira d'Ancona
20127 Milano
Country 60923 0
Italy
Phone 60923 0
+39 0226433160
Fax 60923 0
Email 60923 0
cinque.paola@hsr.it
Contact person for scientific queries
Name 60924 0
Dr Paola Cinque
Address 60924 0
Department of Infectious Diseases
San Raffaele Hospital
Va Stamira d'Ancona
20127 Milano
Country 60924 0
Italy
Phone 60924 0
+39 0226433160
Fax 60924 0
Email 60924 0
cinque.paola@hsr.it