A Clinical Trial to Evaluate the Chronic Safety and Tolerance of Turmipure Gold™ in Healthy Subjects
Condition: Gastrointestinal Tolerance; Liver Function; Kidney Function
Study type: Interventional

Summary: 
      The aim of this study is to evaluate the safety and tolerance of Turmipure Gold™ product
      during a chronic consumption of 5 weeks in healthy subjects. The hypothesis of this study is
      that there are no alterations of the gastrointestinal tolerance, of the haematological and
      biochemical profiles due to Turmipure Gold™ consumption compared to placebo.
    

Detailed description: 
      The rhizome of Curcuma longa (turmeric) is commonly used as a spice and for its medicinal
      proprieties traditionally in Asian countries. Turmeric has been studying in different
      therapeutic area. Antioxidant, anti-inflammatory (respiratory system, joints and digestive),
      antimutagenic, antimicrobial, neurological disease, hepatoprotective and anticancer
      properties are supported by in vitro and in vivo data.

      Despite several data identified in the scientific literature, the community herbal monograph
      of the European Medicines Agency allows the traditional use only for the following
      therapeutic indication "Traditional herbal medicinal product used to increase bile flow for
      the relief of symptoms of indigestion (such as sensation of fullness, flatulence, and slow
      digestion)." According to the World Health Organization (WHO) Monographs on Selected
      Medicinal Plants, the use for treatment of acid, flatulent, or atonic dyspepsia is supported
      by clinical data. Treatment of peptic ulcers, and pain and inflammation due to rheumatoid
      arthritis and of amenorrhoea, dysmenorrhoea, diarrhoea, epilepsy, pain, and skin diseases are
      uses described in pharmacopoeias and in traditional systems of medicine.

      Several health claims are pending for European Commission's decision (referred to the
      Regulation n°1924/2006). As a consequence, in European countries, claims related to
      antioxidant, joints, digestion, liver, etc. are tolerated for the moment.

      Curcumin has been studied as the main bioactive component of turmeric associated to the
      potential health effect. However, besides curcumin, others components have been identified
      called the curcuminoids groups. Curcuminoids are natural yellow-orange pigments and
      hydrophobic polyphenols derived from the rhizome of the herb Curcuma longa. They are commonly
      isolated from the spice and food-coloring agent turmeric. Extracts of curcuminoids generally
      contain 75-80% curcumin, 15-20% demethoxycurcumin (DMC), and 0-10% bisdemethoxycurcumin
      (BDMC).

      Regarding the intrinsic property, curcuminoids have higher solubility in organic solvents
      than in water. As a consequence, curcumin has low aqueous solubility and poor
      gastrointestinal absorption. It was also documented that curcumin have low absorption from
      the gut, rapid metabolism and rapid systemic elimination. This leads to the conclusion that
      turmeric has low bioavailability, which limits its use in general health care and as an
      adjunct in managing various diseases. Indeed, it was found low serum levels and limited
      tissue distribution irrespective of route of administration. In order to improve the
      bioavailability of curcumin, several approaches have been undertaken. The use of adjuvant
      like piperine that interferes with glucuronidation; liposomal curcumin, nanoparticles,
      phospholipid complex; and structural analogues of curcumin. The tested products are different
      from technology of bioavailability enhancement. Recently, Naturex has developed a dried
      emulsion formulation using a turmeric extract mixed together with a quillaja extract,
      sunflower oil and arabic gum. This formulation is highly dispersible in water and should
      therefore improve the bioavailability of curcuminoids.

      In order to assess the bioavailability of the product Turmipure Gold™, Naturex conducted a
      clinical study in 2018. The plasmatic concentration profile of total curcuminoids (curcumin,
      DMC, BDMC and their metabolites) on a 24-hour period after consumption of a single dose of
      300 mg Turmipure Gold™ 30% curcuminoids formulation in comparison to the one obtained after
      consumption of 1500 mg Standard turmeric powder extract 95% curcuminoids was investigated as
      the primary objective (unpublished yet). A statistical significant difference was observed on
      the primary outcome which was the dose-normalized Area Under the Curve (AUC) 0-24h of Total
      curcuminoids. Turmipure Gold™ formulation was significantly higher than Standard turmeric
      powder extract (adjusted p<0.0001) for this parameter.

      Thirty subjects received the products in a cross-over design, 16 women and 14 men and no
      gender effect was observed on the primary outcome.

      Statistical significant differences were also observed on the dose-normalized of Area Under
      the Cuve (AUC0)-24h of Total curcuminoids between products comparisons: Turmipure Gold™ was
      higher than Turmeric extract (1500mg) combined with piperine (15mg) or the phytosome
      formulation (1000mg) (adjusted p<0.0001 for each).

      The aim of this double-blind placebo-controlled clinical trial is to evaluate the chronic
      safety and tolerance of Turmipure Gold™ in healthy subjects during 5 weeks +/- 3 days between
      visit V1 (dispensation of the product) and visit V2 (normal end-of-study). 60 healthy male
      and female volunteers with 40/60 ratio will be recruited for this study.

      In order to assess the gastrointestinal tolerance, a composite score of gastrointestinal
      tolerance has been chosen as primary endpoint of the trial. The composite score of GI
      tolerance will be determined as the sum of the scores of the 4 GI symptoms and the composite
      score of stool frequency and consistency (score of GI tolerance = bloating score + abdominal
      cramping score + stomach noises score + flatulence score + stool score).

      Regarding the safety concern, the European Medicines Agency (EMA) monograph indicate
      contraindication for the following pathologies: "Hypersensitivity to the active substance(s),
      obstruction of bile duct, cholangitis, liver disease, gallstones and any other biliary
      diseases" (confirmed by the WHO monograph). The only undesirable effect reported are "mild
      symptoms of dry mouth, flatulence and gastric irritation may occur. The frequency is not
      known." In addition to this, the safety profile of the comparatives products was assessed
      good in several published trials. This will be investigated deeper in this trial with all the
      safety and tolerance parameters. An additional end-of-study visit could be planned if the
      biological results of the V2 visit are not satisfactory, according to the opinion of the
      investigator.
    

Intervention name(s): Turmipure Gold™; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 30 subjects will take 1000mg in 4 capsules (with 250ml water before breakfast , each day, during 5 weeks; 30 subjects will take 4 capsules with 250ml water before breakfast , each day, during 5 weeks
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This safety and tolerance study is designed as a monocentric, randomized, parallel arms, double-blind, placebo-controlled clinical trial.
Three visits planned: a screening visit (V0) for subjects selection, a randomization visit (V1 with product dispensation, 2 weeks after V0) and a end-of-study visit (V2, 5 weeks after V1). between V1 and V2, a telephone interview will be organized with each subject to evoke the tolerance of the product at mid-term.
An additional end-of-study visit could be planned if the biological results of the V2 visit are not satisfactory, according to the opinion of the investigator.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science