NCT02818283

Soy Modulation of Immune Activation, LDL- Levels, and Lowering Inflammation by Pretzel Isoflavone Dietary Intervention

• Status: Terminated
• Phase: N/A
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Ohio State University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Combination antiretroviral therapy (ART, HIV medications) dramatically increases the expected lifespan of HIV (Human Immunodeficiency Virus)infected patients; yet, the risks for cardiovascular disease (CVD), such as heart attacks and stroke, are increased in this population. This increased risk may be linked to persistent inflammation and activation of the immune system. Although the relationship between cardiovascular disease and HIV-infected individuals who are taking HIV medications is not well understood, the team of researchers involved in this study observed that a diet rich in soy, at levels recommended by the FDA (Federal Drug Administration), improved cholesterol levels and inflammation in individuals not infected with HIV. From this study, the researchers hope to gain understanding on how dietary soy will impact HIV-infected individuals who are taking HIV medications. Two pretzels with and without soy developed at OSU (Ohio State University) in the Department of Food Science and Technology and used in previous clinical trials will be used to investigate how the pretzel snacks will affect your cardiovascular disease risk, immunity, and how your body breaks down naturally occurring chemicals from soy.

Detailed description

This study will significantly advance our knowledge of how dietary soy impacts lipid levels and composition, metabolic parameters and inflammation in HIV+ patients treated with anti-retroviral therapy (ART). HIV+ persons are at increased risk for CVD, and both HIV and ART are associated with metabolic perturbations (including lipid disturbances) and chronic inflammation. There is growing recognition that correcting these perturbations may improve life expectancy. Two clinical trials, first a short-term single armed study, followed by a two armed, placebo controlled, crossover clinical trial, will be used to address the feasibility of a soy-based, functional food intervention and the impact of that intervention on metabolic and immunomodulatory parameters. Daily pretzel dosing of two packets was determined from prior clinical trials with soy bread in patients with prostate cancer. The use of a food-based delivery vehicle has many advantages compared to using a dietary supplement as it provides a strategy to deliver a complexity of bioactive compounds found only in whole food ingredients. We hypothesize that the soy pretzel formulation will be well tolerated with excellent adherence (\>95%) among ART-treated HIV+ patients with moderate hypercholesterolemia. The short-term dose confirmation study (n=20) will be a 6 week study using a single intervention and single dose of soy pretzels to determine Grade 1 and 2 toxicities, compliance, and tolerability of soy pretzels in ART-treated HIV+ patients with moderate hypercholesterolemia. Once, we have confirmed the short-term feasibility of soy pretzels, a subsequent longer-term study will involve a 28 week randomized, placebo-controlled, crossover trial (n=80) with soy and wheat (placebo) pretzels. Overall, the short-term dose confirmation study will provide the necessary clinical data required to move this intervention forward to the long-term placebo controlled trial. Both studies will provide us with valuable biologic material to assess changes in cardiovascular and immune biomarkers relevant to ART-treated HIV+ patients to facilitate future large-scale studies investigating individual differences in soy isoflavone metabolism within this patient population. Specifically, the short-term dose confirmation study will include those participants who are screened and meet eligibility which will be determined using results from a 12 hr fasting lipid panel which includes total cholesterol (TC), low density lipoproteins (LDL), high density lipoproteins (HDL), and triglycerides; health history; and the 2013 American College of Cardiology/ American Heart Association (ACC/AHA) Guidelines cardiovascular risk calculator. Eligible participants will be enrolled and then instructed to follow a legume-free diet (avoid beans, soy beans, lentils, bean sprouts, and peanuts) for two weeks, abstain from other vitamins or dietary supplements, and follow the provided standardized multivitamin regimen. Participants will return to clinic for a fasting blood collection and submit a 24 hour urine collection at week 0. At the end of this visit, participants will be instructed to consume one packet (10 pieces) of soy pretzels twice daily and continue to follow the legume-free diet with the provided multivitamin regimen. Participants will return after 4 weeks to obtain a second month's supply of study agents. Subjects will return after a second 4 weeks for a fasting blood collection and to submit a completed 24 hr urine collection. The subsequent placebo controlled study will include the same criteria used for the earlier short-term study. Participants will be randomized to either a soy pretzel intervention (1 packet of pretzels twice/day: total 20 pieces delivering 24g soy protein and \~60mg isoflavones) or a wheat pretzel intervention (placebo, 1 packet of pretzels twice/day: total 20 pieces containing 0g soy protein and 0mg isoflavones) for 12 weeks before crossing over to the other pretzel intervention for a second 12 weeks. A two-week washout period involving a legume-free diet and standardized multivitamin regimen, similar to the short-term study, will precede each intervention period. Blood and 24-hour urine will be collected at the specified time points to evaluate the sustained effects of the soy pretzel intervention on biomarkers of cardiovascular risk, immune function, and metabolites of isoflavone intervention. This study addresses an innovative approach of utilizing a dietary soy snack food to reduce cardiac risk and to explore multiple drivers of immune activation in HIV disease (pro-inflammatory lipids, microbial translocation, and the cytokines they induce) increasing the likelihood that we will generate results that impact clinically relevant indices of HIV disease progression.

Conditions

• Human Immunodeficiency Virus (HIV) Infection
• Hypercholesterolemia

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Soy Pretzel	Each packet (5oz.) of soy pretzel contains high gluten wheat flour, soy flour, soymilk, vegetable shortening, sugar, yeast, salt, and ascorbic acid. Each packet provides \~280 calories (16% fat, 54% total carbohydrates, and 30% protein).
OTHER	Wheat Pretzel	Each packet (5oz.) of wheat pretzel contains high gluten wheat flour, vital wheat gluten, shortening, sugar, yeast, salt, and ascorbic acid. Each packet provides \~290 calories (16% fat, 54% total carbohydrates, and 30% protein).

Timeline

• Start date: 2016-06-01
• Primary completion: 2023-10-01
• Completion: 2023-10-01
• First posted: 2016-06-29
• Last updated: 2023-10-06

Locations

1 site across 1 country: United States