Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies

August 25, 2017 updated by: Lawson Health Research Institute

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].

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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 [2000] 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:

  1. The Kaiser micronutrient formula [14]: N-Acetyl cysteine (NAC) 300 mg, Acetyl L-carnitine 250 mg, Magnesium 92.5 mg, Alpha lipoic Acid 100 mg, Selenium 13.8 µg, Beta carotene + Vitamin A 5666 IU, Zinc 2.4 mg, Vitamin C 21 mg, Copper 0.225 mg, Vitamin B1 0.3 mg, Boron 0.5 mg, Vitamin B2 0.3 mg, Potassium 1200 mg, Pantothenic acid 1.3 mg, Iron 3.3 mg, Niacinamide 3.8 mg, Manganese 0.5 mg, Inositol 15 mg, Biotin 7.5 µg, Vitamin B6 0.3 mg, Chromium 7.5 µg, Vitamin B12 0.6 µg, Molybdenum 11.3 µg, Vitamin D 52 IU, Choline 121.9 mg, Vitamin E 5.7 IU, Bioflavonoid complex 75 mg, Folic acid 100 µg, L-Glutamine 25 mg, Betaine HCL 37.5 mg;
  2. A multi-component formula containing zinc 30mg, vitamins A + beta carotene 5666 IU , C 21mg and E 5.7 IU, selenium 13.8µg, iron 3.3mg, folic acid 100µg, vitamin B12 0.6 µg, vitamin B6 0.3 mg, vitamin B1 0.3mg
  3. A basic supplement containing zinc 30mg, vitamins A 666 IU, vitamin C 21mg and E 5.7 IU, and folic acid 100µg and 16 mg docosahexaenoic acid (DHA-Omega 3 Fatty Acid) and 24mg eicosapentaenoic acid (EPA-Omega 3 Fatty Acid) [Austin, J. et.al 2006 & Alan DD, et.al 2006].

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 4V2
        • St. Joseph's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Clinically tested CD4 lymphocyte count between 200-400cells/mL (HIV population)
  • Confirmed cancer by physician (cancer population)
  • Confirmed HIV by physician (HIV population)

Exclusion Criteria:

  • Opportunistic infection
  • Mental illness impairing ability to comply with study
  • Pregnancy
  • Currently consuming micronutrient supplement or probiotic
  • Clinical history of lactose-intolerance or cow's milk allergies
  • Require surgery, radiation or chemotherapy during the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SUPPORTIVE_CARE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: 2
Dietary supplement: Probiotic Yogurt D: Placebo -- no added micronutrients
175g/day probiotic yogurt
EXPERIMENTAL: 1
Dietary supplement: Probiotic Yogurt B: with various micronutrients
175g probiotic yogurt / day 25% RDA for each nutrient
Dietary supplement: Probiotic Yogurt A: Kaiser micronutrients
175g probiotic yogurt/ day 25% RDA for each nutrient
Dietary supplement: Probiotic yogurt C: with basic micronutrients
175g yogurt/ day 25% RDA for each nutrient

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Statistically significant improvement of immune status (CD4) Statistically significant improvement of nutritional status
Time Frame: Baseline and Follow-up for each yogurt type
Baseline and Follow-up for each yogurt type

Secondary Outcome Measures

Outcome Measure
Time Frame
Improved quality of life
Time Frame: 4 months
4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lawson Health Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 7, 2007

Primary Completion (ACTUAL)

March 2, 2009

Study Completion (ACTUAL)

March 2, 2009

Study Registration Dates

First Submitted

August 16, 2007

First Submitted That Met QC Criteria

August 16, 2007

First Posted (ESTIMATE)

August 17, 2007

Study Record Updates

Last Update Posted (ACTUAL)

August 28, 2017

Last Update Submitted That Met QC Criteria

August 25, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R-07-220
  • 13468

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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