## Protocol Section
### Identification Module
**NCT ID:** NCT05149079

**Acronym:** MARPEP

**Brief Title:** Effects of a Marine Protein Hydrolysate in Healthy Adults

**Official Title:** Randomized, Double Blind, Placebo Controlled Clinical Study to Investigate the Effect of a Marine Protein Hydrolysate in Healthy Adults

#### Organization Study ID Info
**ID:** FHF-Study
#### Organization
**Class:** OTHER
**Full Name:** University of Bergen
### Status Module
#### Completion Date
**Date:** 2021-05-31

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2021-12-08

**Type:** ACTUAL

**Last Update Submit Date:** 2021-11-25

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2021-05-15

**Type:** ACTUAL

#### Start Date
**Date:** 2021-02-01

**Type:** ACTUAL

**Status Verified Date:** 2021-11

#### Study First Post Date
**Date:** 2021-12-08
**Type:** ACTUAL
**Study First Submit Date:** 2021-03-09
**Study First Submit QC Date:** 2021-11-25
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Haukeland University Hospital

**Class:** OTHER

**Name:** Alesund Hospital

**Class:** OTHER

**Name:** Norwegian University of Science and Technology

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Bergen

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This randomized, double blind, controlled trial investigates changes in the cardiovascular index (triacylglycerol/HDL-cholesterol × waist/hip ratio) after 12 weeks of marine protein hydrolysate (MPH) or whey protein powder (placebo) supplementation in adult healthy persons. Additionally, the study investigates potential effects on plasma parameters of metabolic health including lipids, glucose, inflammatory parameters and redox state, as well as associations between dietary MPH and body weight, abdominal obesity, body composition, and gut microbiota composition. Finally, putative end-products of diet-microbial interactions (TMAO and short-chain fatty acids) with CVD risk factors and biomarkers of mitochondrial function are examined.

**Detailed Description:** Marine protein sources, including fish and fish protein hydrolysates, may have particular health benefits. Health benefits from fish consumption have been attributed to the n-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Proteins from marine sources may contain valuable bioactive components, with amino acid composition and protein profiles that differ from terrestrial sources. Generally, the dietary source of protein can affect cellular energy metabolism, and hydrolyzed peptides can have potent and specific bioactive potential.

Rest raw materials (RRM) from cod (Fjordlaks AS, Norway) are used for the hydrolysis production (Food Grade). Freshly minced RRM were treated with enzymes optimized to generate bioactive hydrolysates using facilities and techniques approved for human consumption. The investigational products are given in a dose of 18 g protein per day, corresponding to the protein content of a standard meal, and similar to doses recommended in a range of protein supplements.

The study enrolls around 70 men and women age of 20-80 years with waist circumference of \< 102 cm for men and \< 88 cm for women. Prospective study participants were informed of the study and invited to participate through advertising primarily in social media (Facebook advertisement, geographically limited to 12 km surrounding the city centers of Bergen and Ålesund). Participants provided written informed consent, and were screened via self-reporting in an online form in EasyTrial hosted by the Research Unit for Clinical Trials at the University of Bergen. Data collection by the study staff at baseline verifies inclusion and exclusion criteria and participant eligibility prior to randomization. The potential participants are informed about practical details at a digital or physical meeting 1-2 weeks prior to baseline.

Groups of participants (40-60% males/females) are block randomized to the two treatments using randomly selected block sizes, and stratified according to sex.

The participants are given a container with the powder sufficient for the entire study period, and a spoon to measure the intake at breakfast (6 g), lunch (6 g) and supper (6 g), or morning (9 g) and evening (9 g) according to individual preference. The patients will mix the powder products in water or mineral water. Flavours have been masked by supplementation with beet powder, and mixing 0.5 g fish hydrolysate per serving in the placebo, to minimize differences in taste of the placebo and active product.

### Conditions Module

**Conditions:**

- Healthy Diet

**Keywords:**

- Cardiovascular disease risk

- Protein supplementation

- Metabolic health

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Randomized, double blind, placebo controlled clinical study

##### Masking Info

**Masking:** TRIPLE

**Masking Description:** The groups will be randomly labelled A or B. Neither participants, care providers or statistician will know the treatments of the groups before the statistical analyses for the primary outcome have been completed.

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 67

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants will consume 18 g of the placebo whey protein supplement each day for 12 weeks.

**Intervention Names:**

- Dietary Supplement: Placebo

**Label:** Placebo (whey protein supplement)

**Type:** PLACEBO_COMPARATOR

#### Arm Group 2

**Description:** Participants will consume 18 g of the cod protein supplement each day for 12 weeks.

**Intervention Names:**

- Dietary Supplement: Cod protein hydrolysate

**Label:** Cod protein hydrolysate supplement

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Cod protein hydrolysate supplement

**Description:** Rest raw materials (RRM) from cod (Fjordlaks AS, Norway) are used for the hydrolysis production (Food Grade). Freshly minced RRM is treated wth enzymes optimized to generate bioactive hydrolysates using facilities and techniques approved for human consumption.

**Name:** Cod protein hydrolysate

**Type:** DIETARY_SUPPLEMENT

#### Intervention 2

**Arm Group Labels:**

- Placebo (whey protein supplement)

**Description:** Whey protein powder, commercially available

**Name:** Placebo

**Other Names:**

- Whey protein powder

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Primary Outcomes

**Description:** Triacylclygerol and HDL-cholesterol concentrations will be measured in serum. Waist and hip circumference will be measured using anthropometric tape over light clothing. For waist circumference, the minimum circumference between the iliac crest and the rib cage will be used. For waist circumference the circumference at the level of the greatest protrusion of the buttocks is used.

**Measure:** Changes in the cardiovascular index (triacylglycerol/high density lipoprotein (HDL)-cholesterol × waist/hip ratio)

**Time Frame:** Baseline to 12 weeks

#### Secondary Outcomes

**Description:** Measured in serum and calculated as 1 / (log(fasting insulin μU/mL) + log(fasting glucose mg/dL)

**Measure:** Changes in the Quick1 index, a surrogate marker of insulin sensitivity

**Time Frame:** Baseline to 12 weeks

**Description:** Measured in serum

**Measure:** Changes in fasting insulin

**Time Frame:** Baseline to 12 weeks

**Description:** Measured in serum

**Measure:** Changes in fasting insulin C-peptide

**Time Frame:** Baseline to 12 weeks

**Description:** Measured in serum

**Measure:** Changes in fasting glucose

**Time Frame:** Baseline to 12 weeks

**Description:** Measured in serum

**Measure:** Changes in total cholesterol

**Time Frame:** Baseline to 12 weeks

**Description:** Measured in serum

**Measure:** Changes in non-high density lipoprotein (HDL) cholesterol

**Time Frame:** Baseline to 12 weeks

**Description:** Measured in serum

**Measure:** Changes in non-esterified fatty acids (NEFA)

**Time Frame:** Baseline to 12 weeks

**Description:** Measured in serum

**Measure:** Changes in triacylglycerol (TAG)

**Time Frame:** Baseline to 12 weeks

**Description:** Measured by 16S sequencing

**Measure:** Changes in gut microbiota composition

**Time Frame:** Baseline to 12 weeks

**Description:** Faecal SCFA concentrations calculated as (mmol/L) × wet faecal weight x faecal moisture content (g/100 g) × 10

**Measure:** Changes in short chained fatty acids (SCFA)

**Time Frame:** Baseline to 12 weeks

**Description:** Body composition measured by bioimpedance analysis

**Measure:** Changes in fat mass/fat free mass ratio

**Time Frame:** Baseline to 12 weeks

**Description:** Waist and hip circumference will be measured using anthropometric tape over light clothing. For waist circumference, the minimum circumference between the iliac crest and the rib cage will be used. For waist circumference the circumference at the level of the greatest protrusion of the buttocks is used

**Measure:** Changes in waist-hip ratio

**Time Frame:** Baseline to 12 weeks

**Description:** Waist circumference will be measured using anthropometric tape over light clothing. Hight will be measured using a stadiometer. For waist circumference, the minimum circumference between the iliac crest and the rib cage will be used.

**Measure:** Changes in waist-to-height ratio (WHtR)

**Time Frame:** Baseline to 12 weeks

**Description:** Blood pressure measurement will be performed manually by a trained nurse using standard equipment

**Measure:** Changes in blood pressure

**Time Frame:** Baseline to 12 weeks

**Description:** Heart rate will be determined manually by a trained nurse

**Measure:** Changes in heart rate

**Time Frame:** Baseline to 12 weeks

**Description:** Measured in plasma by ELISA (enzyme-linked immunosorbent assay)

**Measure:** Changes in glucagon-like peptide 1 (GLP-1, hormone involved in appetite and metabolism regulation)

**Time Frame:** Baseline to 12 weeks

**Description:** Measured in plasma by ELISA (enzyme-linked immunosorbent assay)

**Measure:** Changes in gastric inhibitory polypeptide (GIP, hormone involved in metabolism regulation)

**Time Frame:** Baseline to 12 weeks

**Description:** Measured in plasma by ELISA (enzyme-linked immunosorbent assay)

**Measure:** Changes in ghrelin (hormone involved in appetite regulation)

**Time Frame:** Baseline to 12 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Healthy female and male subjects at age 20-80 years old understanding Norwegian oral and written information
* Waist circumference for males \< 102 cm and females \< 88 cm

Exclusion Criteria:

* Pregnancy or lactation
* Having used high-dose omega-3 PUFA supplements (\>2 g/day) less than 28 days prior to randomization
* Use of corticosteroids that will influence protein metabolism
* Antibiotic treatment previous 3 months
* Alcohol or drug abuse or any conditions associated with poor compliance
* Medical diagnosis of malabsorption disorders, Crohn's disease, or lactose intolerance
* Scheduled hospitalization during the course of the study that could compromise the study
* Diabetes type I or II, serious high blood pressure at screening, serious infections, diseases requiring medication that can influence the study
* Known or suspected sensitivity or allergic reactions to the IMP or excipients
* Presence of other major medical or psychiatric illness that would affect the ability to participate in the study or put the subject at increased risk
* Intake of statins. If needed to obtain the recruitment goals, we will accept people using a low dose of statin

**Healthy Volunteers:** True

**Maximum Age:** 80 Years

**Minimum Age:** 20 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Bergen

**Country:** Norway

**Facility:** Research Unit for Health Trials

**Zip:** 5009

#### Overall Officials

**Official 1:**

**Affiliation:** University of Bergen, Norway

**Name:** Rolf K Berge, PhD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Kim SK, Ngo DH, Vo TS. Marine fish-derived bioactive peptides as potential antihypertensive agents. Adv Food Nutr Res. 2012;65:249-60. doi: 10.1016/B978-0-12-416003-3.00016-0.

**PMID:** 22361192

**Citation:** Erdmann K, Cheung BW, Schroder H. The possible roles of food-derived bioactive peptides in reducing the risk of cardiovascular disease. J Nutr Biochem. 2008 Oct;19(10):643-54. doi: 10.1016/j.jnutbio.2007.11.010. Epub 2008 May 20.

**PMID:** 18495464

## Derived Section

### Intervention Browse Module - Browse Branches

- Abbrev: Ot

- Name: Other Dietary Supplements

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: T435

- Name: Whey Protein

- Relevance: HIGH

- As Found: Ingredients

### Misc Info Module

- Version Holder: 2024-05-24
