Effect of Candida Rugosa Lipase on Serum Triglyceride Lowering

Sponsor

BIO-CAT Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT05295134

Collaborator

Atlantia Food Clinical Trials (Industry), Cork University Hospital (Other)

Enrollment

Location

Arms

7.8

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study was to evaluate the safety and tolerability of 3 doses of fungal lipase in the treatment of adults with mildly elevated serum triglycerides. The secondary objective was to assess the efficacy of fungal lipase in reducing serum triglycerides in adults with mildly elevated serum triglycerides.

Condition or Disease	Intervention/Treatment	Phase
Hypertriglyceridemia	Dietary Supplement: Placebo Dietary Supplement: Candida cylindracea lipase (225,000 FIP lipase units per day) Dietary Supplement: Candida cylindracea lipase (450,000 FIP lipase units per day) Dietary Supplement: Candida cylindracea lipase (675,000 FIP lipase units per day)	N/A

Detailed Description

According to the World Health Organization, ischemic heart diseases and stroke were the leading causes of death globally in 2019, accounting for 16% and 11% of the world's total deaths, respectively. The American Heart Association reported in 2020 that approximately 87% of all strokes are ischemic strokes, in which blood flow to the brain is blocked (Virani et al). That blockage is typically caused by an accumulation of fatty deposits inside triglycerides (atherosclerosis). Higher levels of serum triglycerides are linked to an increased risk of ischemic stroke in men and women. Researchers tracked 7,579 women and 6,372 men whose triglyceride and cholesterol measurements were taken in the late 1970s. Subjects were followed for up to 33 years. During the follow-up period, 837 women and 837 men developed ischemic stroke. Both men and women had a higher risk of stroke with high levels of triglycerides, in particular triglyceride levels of 5 mmol/L (443 mg/dL or 5.0 mmol/L) or more. These individuals carried four-fold greater stroke risk than those with lower levels (Varbo et al).

Each of the current treatments for hypertriglyceridemia has negative side effects and therefore many individuals that suffer from this condition decline treatment to reduce stroke risk. Oral supplementation with a fungal lipase preparation from Candida cylindracea (formerly rugosa), commonly found in dietary supplements for digestive health, is a candidate strategy to lower triglycerides without side effects.

During digestion, each of lingual, gastric, and pancreatic lipases combine to remove the outer 2 fatty acids from ingested, dietary triglycerides, thus forming monoglycerides and 2 free fatty acids. Following uptake by intestinal enterocytes, the free fatty acids are re-esterified with the monoglycerides to reform triglycerides before release in to the bloodstream. Overconsumption of dietary fats can thus lead to elevated levels of serum triglycerides.

Candida cylindracea (formerly rugosa) lipase, however, hydrolyzes all three fatty acids from dietary triglycerides to release free fatty acids and the glycerol backbone. It is predicted that most of these free fatty acids and glycerol molecules enter the bloodstream without reformation to triglycerides by the major metabolic pathway to reform the triglycerides from monoglycerides. Nonetheless, an alternate metabolic pathway to generate triglycerides from free fatty acids alone does exist in enterocytes.

The investigators tested the hypothesis that fungal lipase-mediated lowering of dietary monoglycerides would lower serum triglyceride levels in a randomized, double-blind, placebo controlled parallel arm clinical trial of 39 subjects with elevated serum triglyceride levels. Subjects were between 18 and 75 years of age, with good general health and mildly elevated serum triglycerides (150 mg/dL to 500 mg/dL, or 1.7 mmol/L to 5.6 mmol/L). The study included 4 study site visits over a 13 to 16 week period (including baseline period).

Subjects underwent an initial phone screen and were asked questions regarding their age and general health. Eligible subjects were scheduled for a screening visit. Subjects attend all visits in a fasted state. At the screening visit (Visit 1), the inclusion and exclusion criteria were reviewed and the overall details of the study were explained and informed consent was obtained. Blood pressure, body weight, and body mass index (BMI) were measured. Family and medical history and general health were recorded.

A fasting blood sample was collected and serum triglycerides were measured. Subjects with serum triglyceride levels between 151 mg/dL (1.71 mmol/L) and 499 mg/dL (5.65 mmol/L) were invited to participate in the study. Eligible subjects were scheduled to return to the study site within 4 weeks for their baseline visit (Visit 2).

At Visit 2, a fasting blood sample (12 mL) was collected for glucose, electrolyte, triglyceride, cholesterol (including HDL, LDL, VLDL), liver and kidney function, and HbA1C measurements. Subjects were randomized to one of 4 arms: 1) placebo (n = 9), 2) 1X low-dose (n = 10), 3) 2X medium-dose (n = 10), and 4) 3X high-dose (n = 10). Subjects were provided with a 90 day supply of investigational study product (lipase or placebo) and were instructed to take one dose with each major meal (3 doses per day) for the next 90 days. Subjects were instructed to follow their standard diet and exercise routine for the duration of the study. Subjects were scheduled to return to the study site after 30 days (+/- 4 days) for Visit 3.

At Day 30 (Visit 3), a fasting blood sample (12 mL) was collected for glucose, electrolytes, triglyceride, cholesterol (including HDL, LDL, VLDL), liver and kidney function, and HbA1C measurements. Subjects were scheduled to return to the study site for the 4th and final visit at Day 90. At Day 90, a fasting blood sample (12 mL) was collected for glucose, electrolyte, triglyceride, cholesterol (including HDL, LDL, VLDL), liver and kidney function, and HbA1C measurements. Subjects returned any unused study product and compliance was assessed.

Study Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

A Randomised, Double-Blind, Placebo Controlled, Dose Ranging Study to Investigate the Safety & Efficacy of Candida Rugosa Lipase on Reduction of Serum Triglyceride

Actual Study Start Date :

Mar 13, 2014

Actual Primary Completion Date :

Oct 6, 2014

Actual Study Completion Date :

Nov 4, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Maltodextrin	Dietary Supplement: Placebo Participants were directed to consume 1 placebo capsule containing maltodextrin, three times daily, for 90 days. Subjects were directed to consume the capsules with their three largest eating occasions of the day.
Active Comparator: Lipase: Low-Dose Candida cylindracea lipase (75,000 FIP per serving)	Dietary Supplement: Candida cylindracea lipase (225,000 FIP lipase units per day) Participants were directed to consume 1 capsule containing lipase (75,000 FIP lipase units per capsule), three times daily, for 90 days. Subjects were directed to consume the capsules with their three largest eating occasions of the day. Other Names: GFA-918 Candida rugosa lipase
Active Comparator: Lipase: Medium-Dose Candida cylindracea lipase (150,000 FIP per serving)	Dietary Supplement: Candida cylindracea lipase (450,000 FIP lipase units per day) Participants were directed to consume 2 capsules containing lipase (75,000 FIP lipase units per capsule), three times daily, for 90 days. Subjects were directed to consume the capsules with their three largest eating occasions of the day. Other Names: GFA-918 Candida rugosa lipase
Active Comparator: Lipase: High-Dose Candida cylindracea lipase (225,000 FIP per serving)	Dietary Supplement: Candida cylindracea lipase (675,000 FIP lipase units per day) Participants were directed to consume 2 capsules containing lipase (112,500 FIP lipase units per capsule), three times daily, for 90 days. Subjects were directed to consume the capsules with their three largest eating occasions of the day. Other Names: GFA-918 Candida rugosa lipase

Outcome Measures

Primary Outcome Measures

Safety and tolerability: Adverse events [90 days]
Self-reported adverse events at Visits 1, 2, and 3

Secondary Outcome Measures

The change in levels of fasting serum triglycerides [90 days]
Serum triglycerides (mmol/L)
The change in blood levels of fasting cholesterol [90 days]
HDL cholesterol (mmol/L), LDL cholesterol (mmol/L), and total cholesterol (mmol/L)
Safety: Glycated hemoglobin A1C (HbA1C) [90 days]
Blood HbA1C (mmol/mol)
Safety: Glucose [90 days]
Blood glucose (mmol/L)
Safety: Alanine aminotransferase (ALT) [90 days]
Blood ALT (IU/L)
Safety: Aspartate aminotransferase (AST) [90 days]
Blood AST (IU/L)
Safety: Alkaline phosphatase (ALP) [90 days]
Blood ALP (IU/L)
Safety: Gamma-glutamyl transferase (GGT) [90 days]
Blood GGT (IU/L)
Safety: Sodium [90 days]
Blood sodium (mEq/L)
Safety: Potassium [90 days]
Blood potassium (mEq/L)
Safety: Chloride [90 days]
Blood chloride (mmol/L)
Safety: Calcium [90 days]
Blood calcium (mmol/L)
Safety: Phosphate [90 days]
Blood phosphate (mmol/L)
Safety: Magnesium [90 days]
Blood magnesium (mmol/L)
Safety: Urea [90 days]
Blood urea (mmol/L)
Safety: Creatinine [90 days]
Blood creatinine (umol/L)
Safety: Total protein [90 days]
Blood total protein (g/L)
Safety: Albumin [90 days]
Blood albumin (g/L)
Safety: Globulin [90 days]
Blood globulin (g/L)
Safety: Total bilirubin [90 days]
Blood total bilirubin (umol/L)
Safety: Uric acid [90 days]
Blood uric acid (umol/L)
36-Item Short Form Health Survey (SF-36) [90 days]
Physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH), physical component summary (PCS), mental component summary (MCS)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Be able to give written informed consent
Be between 18 and 75 years of age
Be in generally good health as determined by the investigator
Serum triglyceride levels between 151 mg/dL (1.71 mmol/L) and 499 mg/dL (5.65 mmol/L)

Exclusion Criteria:

Are less than 18 and greater than 75 years of age
Females are pregnant, lactating or wish to become pregnant during the study
Are hypersensitive to any of the components of the test product,
Have a significant acute or chronic, unstable and untreated disease or any condition which contraindicates, in the investigator's judgement, entry to the study
Have an active gastrointestinal disorder or previous gastrointestinal surgery
Have a known family history of hyperlipidemia
Having a condition or have taken a medication or supplement that the investigator believes would interfere with the objectives of the study, pose a safety risk or confound the interpretation of the study results, including triglyceride lowering medications (e.g., fibrates and statins) and supplements (e.g., plant sterols/stanols, fish oil supplements, and vitamin B complex supplements)
Have not made any major dietary changes in the past 3 months
History of illicit drug use
Subjects who, in the opinion of the investigator, are considered to be poor attendees or unlikely for any reason to be able to comply with the trial
Subjects may not be receiving treatment involving experimental drugs
If the subject has participated in a recent experimental trial, the trial must have been completed not less than 60 days prior to this study
Have a malignant disease or any concomitant end-stage organ disease