Hemp Seed Protein and Bioactive Peptides Consumption for Hypertension

Double-blind, Randomized, Cross-over Trial of Whole Hemp Seed Protein and Hemp Seed Protein Hydrolysate Derived Bioactive Peptide Consumption for Hypertension

This clinical trial is being conducted to study the effect of whole hemp seed protein, hemp seed protein hydrolysate derived bioactive peptide and casein protein consumption on systolic and diastolic ambulatory blood pressure. This study is will be conducted in 35 hypertensive participants aged between ≥18 and ≤75 yrs who have systolic blood pressure higher than 130 mmHg or diastolic blood pressure ≤ 110 mmHg. The study will consist of 3 periods of 42 days each during which participants will consume assigned treatment. Consumption of treatments will be from days 1 to 42. There will also be a washout period of a minimum of 14 days between the 3 treatment periods where the participants can consume their habitual diets. The entire study is designed to take 22 weeks from start to completion. The participants will consume the assigned treatment twice a day. The treatments are in the form of a smoothie and the smoothies will consist of frozen fruit, fruit juice, frozen yoghurt/sorbet, and 25 g of protein from treatment protein powder which is 25 grams of casein protein, 25 grams of hemp seed protein, or 22.5 grams of hemp seed protein and 2.5 grams of hemp seed protein hydrolysate derived bioactive peptides. On days 1 and 42 of each treatment period of the trial, body weight, waist and hip circumference, blood pressure, pulse wave velocity (PWV) and augmentation index (AI) will be measured. Ambulatory blood pressure (ABP) over 24 hours will also be measured on day 1 of phase 1 and day 42 of each treatment period of the trial.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Other: Whole hemp seed protein; Other: Whole hemp seed protein plus bioactive peptides; Other: Casein protein

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3T 6C5
      • Richardson Centre for Food Technology and Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• BMI: 18.5-40 kg/m2
• Systolic blood pressure between 130-160 mmHg
• Diastolic blood pressure ≤ 110 mmHg
• Ability and willingness to give informed consent to participate in the trial
• Willingness to complete questionnaires, records, and diaries associated with the study and to complete all clinic visits
• Willingness to fast 10-12 hours before blood samples and abstain from alcohol two days prior to blood sampling and BP measurement and abstain from coffee and physical exercise at least 14 and 4 hours before measurement respectively
• Negative pregnancy test for women with child-bearing potential

Exclusion Criteria:

• Unable to speak/read in English
• Active cardiovascular disease including stroke, congestive heart failure, myocardial infarction, unstable angina pectoris, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, temporal ischemic attacks, secondary hypertension, type 1 or type 2 diabetes, anemia, abnormal electrolytes, proteinuria, and abnormal liver, kidney or thyroid function
• History of cancer or malignancy in the last 5 years, or any metabolic disease, gastrointestinal disorder or other clinically significant disease/disorder which could interfere with the results of the study or the safety of the participant
• Taking lipid or blood pressure lowering medications or any type of supplements for less than 3 months (Note: all medications or supplements will be permitted if they are on a stable dose for more than 3 months before the start of the study)
• Smokers, tobacco/snuff/nicotine users, recreational drug users
• Consuming more than 14 alcoholic beverages a week
• Any dietary restrictions preventing from consuming the trial treatments
• Weight gain or loss greater than 5 kg in the past three months
• Exercising > 15 miles/wk or 4,000 kcal/wk
• Known to be pregnant or breast-feeding or planning on becoming pregnant during the trial period
• Having clinically significant biochemistry defined as: Sodium: <134 mmol/l, >148 mmol/l; fasting glucose: > 6.1 mmol/L; LDL-C ≥4.9 mmol/L or any other clinically significant abnormality in hematology and/or biochemistry at the investigator's discretion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Whole hemp seed protein; 25 grams of hemp seed protein powder, twice a day	Other: Whole hemp seed protein; The intervention was provided in the form of a smoothie.
Experimental: Whole hemp seed protein plus bioactive peptides; 22.5 grams of hemp seed protein and 2.5 grams of hemp seed protein hydrolysate derived bioactive peptides, twice a day	Other: Whole hemp seed protein plus bioactive peptides; The intervention was provided in the form of a smoothie.
Active Comparator: Casein protein; 25 grams of protein powder, twice a day	Other: Casein protein; The intervention was provided in the form of a smoothie.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 24 hour ambulatory blood pressure	Participants were fitted with an ambulatory blood pressure monitor (ABPM) for 24 hours. Continuous diastolic and systolic blood pressure were measured over 24 hours.	Measured at day 1 of phase 1 (baseline) and change from baseline ABP at week 6 of phase 1, 2 and 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in angiotensin-converting enzyme (ACE) activity in the plasma	Measured using spectrophotometric method with furanacryloyl-L-phenylalanylglycylglycine (FAPGG) as substrate	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline plasma ACE activity at day 42 of phase 1, 2 and 3
Change in nitric oxide (NO) plasma concentrations	Was determined in plasma using nitrate/nitrite colorimetric assay kit (Cayman Chemical, Michigan, USA)	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline plasma NO concentration at day 42 of phase 1, 2 and 3
Change in serum renin concentration	Measured using a fluorometric microplate reader (Spectra MAX Gemini, Molecular Devices, Sunnyvale, CA).	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline serum renin concentration at day 42 of phase 1, 2 and 3
Change in plasma reactive oxygen and nitrogen species (ROS/RNS) concentration	Was determined using OxiSelec ROS/RNS assay kit and fluorescence plate reader at 480 nm excitation / 530 nm emission	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline ROS/RNS concentration at day 42 of phase 1, 2 and 3
Change in plasma total peroxides (PTPs) concentration	Was determined using microplate reader at 500 nm	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline PTPs concentration at day 42 of phase 1, 2 and 3
Change in plasma superoxide dismutase (SOD) concentration	SOD OxiSelect assay kit (Cell Biolabs, Inc., San Diego, CA, USA) and microplate reader at 490 nm were used for this assay	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline plasma SOD concentration at day 42 of phase 1, 2 and 3
Change in plasma catalase (CAT) concentration	CAT assay kit (Cell Biolabs, Inc. San Diego, CA, USA) and fluorescence microplate reader at excitation and emission 550 and 590 nm were used for this assay	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline plasma CAT concentration at day 42 of phase 1, 2 and 3
Change in plasma free oxylipin concentrations	HPLC/MS/MS by using a Luna 5μm C18 column on a Shimadzu Nexera XR HPLC, coupled to an ABSciex QTRAP 6500 MS	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline plasma free oxylipin concentrations at day 42 of phase 1, 2 and 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood pressure	Systolic and diastolic blood pressure were measured using an automated oscillometric measurement device in an office setting in a quiet room while the participant wass in a seated position and arm rested on an arm rest at heart level. Participants were advised to rest quietly throughout the measurements. Measurements were performed 4 times at 2-minute intervals.	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline blood pressure at week 3 and 6 of phase 1, 2 and 3
Change in pulse wave velocity (PWV)	Measured using an automated oscillometric measurement device (Mobil-O-Graph, IEM, Stolberg, Germany) in an office setting in a quiet room while the participant was in a seated position and arm rested on an arm rest at heart level. Participants were advised to rest quietly throughout the measurements.	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline PWV at week 6 of phase 1, 2 and 3
Change in augmentation index (AI)	Measured using an automated oscillometric measurement device (Mobil-O-Graph, IEM, Stolberg, Germany) in an office setting in a quiet room while the participant was in a seated position and arm rested on an arm rest at heart level. Participants were advised to rest quietly throughout the measurements.	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline AI at week 6 of phase 1, 2 and 3
Change in body weight	Following standardized procedures	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline body weight at week 6 of phase 1, 2 and 3
Change in waist circumference	Following standardized procedures	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline waist circumference at week 6 of phase 1, 2 and 3
Change in hip circumference	Following standardized procedures	Measured at day 1 of phase 1, 2 and 3 (baseline) and change from baseline hip circumference at week 6 of phase 1, 2 and 3
Change in body composition	Looking at potential changes in body fat and lean mass composition by Dual X-ray absorptiometry (DXA). For this procedure, the participant were needed to lie in a horizontal position for about 5-15 minutes while the scan arm passes from the head to the feet. The radiation from this test was very low dosage (equivalent to approximately 1 day of natural background radiation).	Measured at day 1 of phase 1 (baseline) and change from baseline body composition at week 6 of phase 1, 2 and 3

Collaborators and Investigators

• Sponsor: University of Manitoba
• Collaborators: Heart and Stroke Foundation of Canada; Manitoba Harvest
• Investigators: Principal Investigator: Rotimi Aluko, PhD, University of Manitoba

Publications and helpful links

General Publications

• Samsamikor M, Mackay D, Mollard RC, Aluko RE. A double-blind, randomized, crossover trial protocol of whole hemp seed protein and hemp seed protein hydrolysate consumption for hypertension. Trials. 2020 Apr 23;21(1):354. doi: 10.1186/s13063-020-4164-z.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2018
• Primary Completion (Actual): November 15, 2019
• Study Completion (Actual): November 15, 2019

Study Registration Dates

• First Submitted: March 29, 2018
• First Submitted That Met QC Criteria: April 24, 2018
• First Posted (Actual): April 26, 2018

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: High blood pressure; Hemp seed protein; Protein hydrolysate; Bioactive peptides; Cannabis sativa
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Caseins
• Other Study ID Numbers: HS20390 (B2016:125)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No