Processing Responses of Grains (PRO-Grains) Study

• Sponsor: Boston Children's Hospital (Other)
• Overall Status: Withdrawn
• CT.gov ID: NCT02186353
• Collaborator: Kansas State University (Other)
• Enrollment: 0
• Location: 1
• Arms: 3
• Duration (Months): 12
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of this pilot study will be to examine the effects of consuming whole grains, differing in the degree of processing, on insulin sensitivity and other cardiometabolic risk factors. The overall aim will be to assess feasibility of the test diets and to generate preliminary data.

Condition or Disease	Intervention/Treatment	Phase
Insulin Resistance; Cardiovascular Disease; Diabetes	Behavioral: Partial feeding study	N/A

Detailed Description

In this pilot study, the investigators will access feasibility and generate preliminary data to systematically address a major question in nutrition: Does food processing, specifically with regard to whole grains (WGs), have an independent effect on outcomes related to diabetes and cardiovascular disease? Whole grains are defined as intact, ground, cracked, or flaked caryopsis (kernel or seed), where the principal components (bran, endosperm, germ) are present in the same proportion as the intact caryopsis. In contrast, refined grains (RGs) are milled to remove the bran and germ, leaving only the endosperm and resulting in lower fiber, iron, and many B vitamins. Several previous studies have shown that consumption of WGs vs. RGs improves insulin sensitivity and decreases risk for chronic disease. However, the effects of consuming WGs may differ depending on degree of processing. While whole grain products contain the three components of the kernel, we hypothesize that consuming the food containing the least processed (and least pulverized) kernels may have beneficial effects on metabolism that decrease disease risk through plausible physiological mechanisms.

The investigators propose a partial feeding study using a randomized 3-period crossover design to compare the effects of 1) intact or minimally processed whole grains, 2) highly processed whole grains, and 3) refined grains, each fed for 4 weeks. The primary outcome will be change in peripheral insulin sensitivity. Secondary outcomes include hepatic insulin sensitivity, components of the metabolic syndrome and other cardiometabolic risk factors, arterial stiffness, gut microbiome and fecal short chain fatty acids, and ratings of hunger, satiation, palatability, and acceptability (gastrointestinal symptoms).

Study Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Intact vs. Highly Processed Whole Grains on Insulin Sensitivity and Other Cardiometabolic Risk Factors in Hyperinsulinemic Adults
• Study Start Date: Sep 1, 2014
• Anticipated Primary Completion Date: Sep 1, 2015
• Anticipated Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intact/minimally processed whole grains Partial feeding study	Behavioral: Partial feeding study; Provision of all grain foods where only the processing of kernels used to produce the grain foods will differ among test diets. Each participant will be assigned to complete the three 4-week test diets in random sequence.
Experimental: Highly processed whole grains Partial feeding study	Behavioral: Partial feeding study; Provision of all grain foods where only the processing of kernels used to produce the grain foods will differ among test diets. Each participant will be assigned to complete the three 4-week test diets in random sequence.
Active Comparator: Refined grains Partial feeding study	Behavioral: Partial feeding study; Provision of all grain foods where only the processing of kernels used to produce the grain foods will differ among test diets. Each participant will be assigned to complete the three 4-week test diets in random sequence.

Outcome Measures

Primary Outcome Measures

1. Change from week 0 in peripheral insulin sensitivity (assessed by frequently-sampled oral glucose tolerance test) at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

2. Change from week 0 in peripheral insulin sensitivity (assessed by frequently-sampled oral glucose tolerance test) at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

3. Change from week 0 in peripheral insulin sensitivity (assessed by frequently-sampled oral glucose tolerance test) at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

Secondary Outcome Measures

1. Change from week 0 in hepatic insulin sensitivity (assessed by frequently-sampled oral glucose tolerance test) at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

2. Change from week 0 in hepatic insulin sensitivity (assessed by frequently-sampled oral glucose tolerance test) at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

3. Change from week 0 in hepatic insulin sensitivity (assessed by frequently-sampled oral glucose tolerance test) at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

4. Change from week 0 in fasting glucose at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

5. Change from week 0 in fasting glucose at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

6. Change from week 0 in fasting glucose at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

7. Change from week 0 in fasting insulin at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

8. Change from week 0 in fasting insulin at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

9. Change from week 0 in fasting insulin at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

10. Change from week 0 in blood lipids at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

11. Change from week 0 in blood lipids at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

12. Change from week 0 in blood lipids at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

13. Change from week 0 in high-sensitivity C-reactive protein at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

14. Change from week 0 in high-sensitivity C-reactive protein at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

15. Change from week 0 in high-sensitivity C-reactive protein at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

16. Change from week 0 in plasminogen activator inhibitor-1 (PAI-1) at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

17. Change from week 0 in plasminogen activator inhibitor-1 (PAI-1) at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

18. Change from week 0 in plasminogen activator inhibitor-1 (PAI-1) at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

19. Change from week 0 in alanine aminotransferase (ALT) at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

20. Change from week 0 in alanine aminotransferase (ALT) at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

21. Change from week 0 in alanine aminotransferase (ALT) at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

22. Change from week 0 in serum metabolomics profile at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

23. Change from week 0 in serum metabolomics profile at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

24. Change from week 0 in serum metabolomics profile at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

25. Change from week 0 in blood pressure at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

26. Change from week 0 in blood pressure at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

27. Change from week 0 in blood pressure at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

28. Change from week 0 in waist circumference at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

29. Change from week 0 in waist circumference at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

30. Change from week 0 in waist circumference at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

31. Change from week 0 in arterial stiffness (assessed by carotid-femoral pulse wave velocity) at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

32. Change from week 0 in arterial stiffness (assessed by carotid-femoral pulse wave velocity) at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

33. Change from week 0 in arterial stiffness (assessed by carotid-femoral pulse wave velocity) at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

34. Change from week 0 in gut microbiome composition (16s rRNA sequencing) and fecal short chain fatty acids at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

35. Change from week 0 in gut microbiome composition (16s rRNA sequencing) and fecal short chain fatty acids at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

36. Change from week 0 in gut microbiome composition (16s rRNA sequencing) and fecal short chain fatty acids at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

37. Change from week 0 in ratings of hunger and satiation at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

38. Change from week 0 in ratings of hunger and satiation at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

39. Change from week 0 in ratings of hunger and satiation at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

40. Change from week 0 in ratings of palatability and acceptability (gastrointestinal symptoms) at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

41. Change from week 0 in ratings of palatability and acceptability (gastrointestinal symptoms) at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

42. Change from week 0 in ratings of palatability and acceptability (gastrointestinal symptoms) at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

43. Change from week 0 in body weight at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

44. Change from week 0 in body weight at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

45. Change from week 0 in body weight at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

46. Change from week 0 in dietary intake at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

47. Change from week 0 in dietary intake at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

48. Change from week 0 in dietary intake at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

49. Change from week 0 in physical activity (assessed by accelerometry) at week 4 [Week 0, Week 4 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

50. Change from week 0 in physical activity (assessed by accelerometry) at week 8 [Week 0, Week 8 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

51. Change from week 0 in physical activity (assessed by accelerometry) at week 12 [Week 0, Week 12 (End of 4-week diet of intact/minimally processed whole grains OR highly processed whole grains OR refined grains)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Aged 18 to 35 years

• Body mass index ≥ 25 and <40 kg/m2

• Serum fasting insulin >10 uIU/mL and one of the following metabolic syndrome components: waist circumference, men: ≥102 cm, women: ≥88 cm; triglycerides, ≥150 mg/dL; HDL-C, men: <40 mg/dL , women: <50 mg/dL; systolic blood pressure ≥130 or diastolic blood pressure ≥85 mmHg; or fasting glucose, ≥100 mg/dL

• Medical clearance from a primary care provider to rule out any major medical illness, disability, or disorder (e.g., liver disease, renal failure, cancer)

• Access to a working telephone or cell phone

• Willingness to eat the grain foods provided during participation

• If female, regular menstrual cycles (defined as 26-30 days, ±1 day full flow, i.e. 26 to 30 days between cycles; no more than one day variation in the duration of menstrual flow)

Exclusion Criteria:

• Pre-existing major medical illness by medical history or laboratory screening tests

• Allergy or sensitivity to gluten (self-reported or physician diagnosed)

• 5% change in weight within previous 6 months

• Current smoking (1 cigarette in the past week)

• Major surgery within the previous 6 months

• Physical, mental, or cognitive handicaps that prevent participation.

• Alcohol intake >7 drinks per week

• Use of medications that may affect study outcomes

• Use of antibiotics within the previous 3 months (in those who agree to complete the analyses of gut microbiome and fecal short chain fatty acids)

• Use of illegal drugs

• Plans to be away from home for 1 week or longer during the study period (e.g., vacation, relocation)

• Another member of the family (first degree relative) or household participating in the study

• If female, pregnancy or lactation during prior 12 months, plans to become pregnant during the study period, change in oral contraceptives within 3 months, or irregular menstrual cycle frequency (<10 bleeds/year)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Boston	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Boston Children's Hospital
• Kansas State University

Investigators

• Principal Investigator: Julia MW Wong, PhD, RD, Boston Children's Hospital
• Study Chair: David S Ludwig, MD, PhD, Boston Children's Hospital
• Study Chair: Cara B Ebbeling, PhD, Boston Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Julia Wong, Instructor in Pediatrics, Boston Children's Hospital
• ClinicalTrials.gov Identifier: NCT02186353
• Other Study ID Numbers: P00009343
• First Posted: Jul 10, 2014
• Last Update Posted: Apr 11, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Julia Wong, Instructor in Pediatrics, Boston Children's Hospital: Whole grains; Food processing; Cardiometabolic risk factors
• Additional relevant MeSH terms: Cardiovascular Diseases; Insulin Resistance

Study Results

No Results Posted as of Apr 11, 2017