Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies
Recruitment status was: Active, not recruiting
|First Received Date ICMJE||August 16, 2007|
|Last Updated Date||July 6, 2009|
|Start Date ICMJE||September 2007|
|Estimated Primary Completion Date||August 2008 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Statistically significant improvement of immune status (CD4) Statistically significant improvement of nutritional status [ Time Frame: Baseline and Follow-up for each yogurt type ] [ Designated as safety issue: Yes ]|
|Original Primary Outcome Measures ICMJE
||Statistically significant improvement of immune status Statistically significant improvement of nutritional status [ Time Frame: 4 months ]|
|Change History||Complete list of historical versions of study NCT00517803 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Improved quality of life [ Time Frame: 4 months ] [ Designated as safety issue: No ]|
|Original Secondary Outcome Measures ICMJE
||Improved quality of life [ Time Frame: 4 months ]|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies|
|Official Title ICMJE||Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies: A Randomized, Placebo-Controlled Trial|
We hypothesize that micronutrient fortified probiotic yogurt can improve nutritional status and enhance immunity parameters in subjects HIV/AIDS and other immunodeficiencies.
We have developed a micronutrient-fortified probiotic yogurt that has safe and beneficial levels of micronutrients for human consumption. This has been undertaken with the guidance of Edward Farnworth, a senior research scientist at Agri-Food Canada-Food Research and Development Centre, St. Hyacinthe, Quebec
We will now measure nutritional parameters (height, weight, serum albumin, serum nutrient levels, blood urea, liver function tests (AST, ALT)) to determine if there is a statistically significant difference between the various levels of fortified probiotic yogurt and the placebo on the nutritional parameters of the subjects consuming the yogurt.
We will measure immunological parameters (CD4 lymphocyte count, CBC, levels of TNFα, IL-12, IL-10, and G-CSF [Kim, et.al. 2006]) in order to determine if there is a statistically significant difference using fortified probiotic yogurt compared to a placebo.
In addition, we will determine if the micronutrient-fortified probiotic yogurt has a significant impact on the overall quality of life for the subjects using the "linear analogue self assessment" tool [Kaiser, et.al 2006].
Drs. Reid and Hekmat have recently developed a fermented milk product (yogurt) containing Lactobacillus GR-1 and RC-14 and concluded that such dairy products are suitable vehicles for these beneficial microorganisms [Hekmat, S. & Reid, G. 2006].
The strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 have a proven efficacy to treat and protect against gastrointestinal and urogenital infections [Anukam, K. et. al. 2006; 2007]. In one study, the supplementation of yogurt with these probiotics was shown to eradicate diahrea and increase the CD4 T-lymphocyte counts in HIV subjects [Anukam, K. et.al. 2006]. HIV infected subjects often suffer diarrheal episodes, and consequently experience malabsorption of certain nutrients [Cunningham-Rundles, 2000]. A study conducted by Cunningham et. al  found that probiotic Lactobacillus plantarum 299 had a positive impact on the immunity of 10/17 children and on the growth of all of the children who were HIV-positive.
It is estimated that 75 percent of immune function is localized in the gastrointestinal tract, which may explain why oral administration of probiotics is an excellent tool for immunomodulation [Olah, A. et. al. 2002]. In a study of 45 patients with acute pancreatitis, 22 were given probiotic Lactobacillus plantarum 299 and 10g of oat fibre with regular enteral nutrition; and 23 were given a placebo in the form of regular enteral nutrition. Significantly fewer (n=1 versus n=7) patients in the probiotic/fibre group experienced septic complications requiring surgery, highlighting the safety and potential hospitalized benefits that could be accrued for critical care nutrition.
A study has recently shown in 40 HIV-infected patients taking a stavudine and/or didanosine-based HAART regimen plus micronutrients twice daily for twelve weeks, that the absolute CD4 count increased by an average of 24% versus 0% in the placebo group (p=0.01). The mean HIV-1 RNA decreased in the micronutrient supplementation group [Kaiser, et.al. 2006]. This is significant for the HIV/AIDS pandemic in Africa and for the many people in Canada living with HIV/AIDS. In addition, this may be related to other immunodeficiencies in hospitalized patients from chemotherapeutic and radiological treatments, organ transplantation, controlling diabetes, and other chronic ailments.
Clinical malnutrition is a heterogenous group of disorders including macronutrient deficiencies that lead to body cell mass depletion and micronutrient deficiencies, and these often coexist with infectious and inflammatory processes [Hughes,S. & Kelly, P. 2006]. Diverse factors affect bioavailability, such as the nutritional status of individuals, the presence in the diet of substances which facilitate or inhibit its absorption, interactions among micronutrients, illnesses, and chemical characteristics of the compound used for fortification. There is good evidence that specific micronutrients, particularly zinc and vitamin A, influence immunity, while iron supplementation is often not effective in Africa [Hughes, S. & Kelly, P. 2006].
More than 20% of older adults may have marginal or frank vitamin B12 deficiency [Park, et.al. 2006], while folic acid is often deficient in children and reproductive aged females. Glutamine, arginine, fatty acids, and vitamin E provide additional benefits to immunocompromised persons or patients who suffer from various infections, while long-chain polyunsaturated n-3 fatty acids, vitamin E, vitamin C, selenium, and nucleotides can modulate immunity to fight infection [Field, et.al. 2002]. In order to produce energy, the use of glucose by nervous tissue requires vitamin B1; this vitamin modulates cognitive performance, especially in the elderly. Vitamin B9 preserves brain during its development and memory during ageing. Vitamin B6 is likely to benefit in treating premenstrual depression. Vitamins B6 and B12, among others, are directly involved in the synthesis of some neurotransmitters [Bourre, JM. 2006]. Thus, three formulations added to L. rhamnosus GR-2 supplemented yogurt, will be tested at the Brescia College Tasting Centre where volunteers will score the products for taste and texture [Hekmat, S. & Reid, G. 2006]
Thirty test subjects will be recruited during the first four months of the study, for inclusion in a trial starting at the 4-6 month time-point, with completion by 10-12 months. A crossover study will be performed in London in which 10 HIV positive volunteers with CD4 counts between 200 and 400 on their standard treatment (including Highly Active Antiretroviral Therapy), and 10 subjects with Cancer who are in the recovery stages and not currently receiving chemotherapy or radiation therapy, and 10 healthy adults (aged 18-30) will randomly be assigned to receive one cup of Yogurts 1, 2 or 3 and a control unsupplemented yogurt 4, daily for one month, followed by a two week washout where no yogurt will be consumed, then one month on the second yogurt, two weeks off etc for 162 days. Subjects will not be receiving antibiotics, not have any mental illness that would affect compliance, or not be requiring surgery during the study. No restrictions will be placed on subjects continuing prescribed or other remedies, but none will consume any other probiotic product during the study. The volunteers will be gender matched and a randomization scheme will ensure that subjects are blinded and different yogurts are distributed at each time (thus, for example two subjects will receive yogurt 1, two yogurt 2, three yogurt 3 and three yogurt 4 on day sample day one). The two week washout period will be used, as probiotic organisms do not persist for longer than that. Various measurements will be taken on the day of consuming the first and last batches of yogurt (days 0, 30, 44, 74, 88, 118, 132, 162). These will include weight, height, and from blood samples the CD4 count, CBC, levels of TNFα, IL-12, IL-10 and G-CSF [Kim, et.al. 2006], liver function test (AST, ALT), serum albumin, total protein, blood urea, serum zinc levels, serum selenium levels and HIV-1 RNA. A linear analogue self-assessment tool will be used to assess the subject's energy levels, daily activities and overall quality of life [Kaiser, et.al. 2006].
The present project is an important step in developing new yogurts, supplemented with micronutrients and probiotic lactobacilli for malnourished children, adults, and seniors in Canada, as well as surgical, transplant, and hospitalized patients, and HIV/AIDS subjects in Canada and in Africa. The following formulations will be used to supplement the yogurt:
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
|Study Arm (s)||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Enrollment ICMJE||30|
|Estimated Completion Date||August 2009|
|Estimated Primary Completion Date||August 2008 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 85 Years (Adult, Senior)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Canada|
|Removed Location Countries|
|NCT Number ICMJE||NCT00517803|
|Other Study ID Numbers ICMJE||R-07-220, 13468|
|Has Data Monitoring Committee||Yes|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Dr. Gregor Reid, University of Western Ontario|
|Study Sponsor ICMJE||Lawson Health Research Institute|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Lawson Health Research Institute|
|Verification Date||July 2009|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP