Nutritional Trial With Probiotic Fortified Milk in Women Affected by Insomnia

Sleep Disorders Clinical Trial

— Prosit  

Official title:

Promotion of Consumer's Health: Nutritional Enhancement/Valorization of Agrofood Italian Traditional Products (PROS.IT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03985228
• Other study ID #: MIUR prot.n.257/Ric.
• Status: Completed
• Phase: N/A
• Start date: November 20, 2015
• Est. completion date: August 31, 2017

Study information

• Verified date: June 2019
• Source: University of Bologna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study "Nutritional Trial With Probiotic Fortified Milk in Women Affected by Insomnia" is a part of a complex and multi-sectoral development research project (PROS.IT) with the participation of University Research Institutes and small/medium Italian enterprises.

The general objective of the Project is to promote the collaboration between the best scientific research, both epidemiological and experimental, and the most advanced technologies to develop fortified foods that meeting the specific nutritional requirements of adult consumers. This objective will be achieved by the nutritional improvement of primary production, the development of innovative functional foods at high added value, in addition to traditional products functionalized, which are peculiar of the Italian local districts.

Description:

Sleep disorders and, in particular, insomnia, are quite common conditions in over 55 population, especially among women. Insomnia becomes a chronic pathology when the difficulty in initiating or maintaining sleep occurs more times a week for several months and is associated to a constant feeling of fatigue, concentration problems, mood disorders and social and family troubles severely impairing the quality of life. In according to the sleep hygiene guidelines, the therapeutic treatments for insomnia include drugs (benzodiazepines, non-benzodiazepines, antidepressants) with often not fully satisfactory results for the patient and entailing a series of side effects, such as daytime sleepiness, lack of attention and energy in addition to mental confusion. Recently, some researches in neurological field have shown that disorders affecting central nervous system, as well as sleep and circadian rhythm disruption, can be associated to specific alteration of the gut microbiota. The enteric nervous system has been referred to as a "second brain" able to interact with the central nervous system impinging upon higher cognitive functions through a bidirectional communication system known as gut-brain axis. The gut microflora plays a crucial role in gut-brain axis, modulating stress response through the Hypothalamic-Pituitary-Adrenal axis and thus influencing memory, mood, cognition and sleep architecture. Therefore, a non-pharmacological intervention aimed to improve gut microbiota and the inflammatory bowel conditions could be an effective strategy to counteract insomnia. In the framework of Pros.IT project, the Granarolo S.p.A. in collaboration with the University of Bologna has developed a milk enriched with different micronutrients (vitamins, ω-3 fatty acids, prebiotics, curcumin) and "infant-type" probiotics isolated from human milk and endowed with immunomodulating activity. This supplementation should improve the overall health status, and in particular the plant extracts, prebiotics and probiotics with anti-inflammatory and immunomodulatory activities should ameliorate significantly sleep quality and stress perception through the modulation of gut microbiota and gut-brain axis.

The main goal of this study is to evaluate the effect of the administration of a functional milk reinforced with probiotics (250ml/die), vitamins and other micronutrients on sleep of patients suffering from chronic insomnia. An objective assessment it requires a value at least higher than 3% of increase of the sleep efficiency, since the 3% is the percentage of improvement recognized to the common drugs against insomnia. The study is randomized, double-blind, placebo-controlled trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: August 31, 2017
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 55 Years to 70 Years

Eligibility

Inclusion Criteria:

• Subjects with an age between 55 and 70 years old, only females, free-living, affected by chronic insomnia defined according to the criteria of the International Classification of Sleep Disorders (2014).

Exclusion Criteria:

• Allergy or intolerance to cow's milk. Use of Benzodiazepines, "Z drugs" or anti-depressive drugs during the three months preceding the start of the trial. Celiac disease and other intestinal malabsorption or inflammatory bowel diseases (Crohn's disease and ulcerative colitis). Chronic therapy with anticoagulant, corticosteroid, anticancer drugs and immunosuppressants. Diabetes type I and type II, chronic viral hepatitis, neurological disorders or dementia, cancer, poor prognosis disease in the short term. Use of anti-inflammatory drugs or inflammatory-infective events within 7 days before the start of the trial and use of antibiotics or vaccinations within 30 days before.

Related Conditions & MeSH terms

• Parasomnias
• Sleep Disorders
• Sleep Wake Disorders

Intervention

Dietary Supplement:
• Fortified milk
Ultra high temperature UHT, partly-skimmed milk (1% fat), highly digestible (lactose <0.01%), enriched in whey protein (5%) and calcium (0.24%), supplemented with unsaturated fatty acids omega-3 (DHA + EPA), vitamins (D, B12, B6, B9, E, C), prebiotics (FOS) and phyto curcuminoids (sunflower lecithin). Milk had to be associated with a packet of lyophilized and concentrated probiotics (Bifidobacteria infant-type and / or Lactobacilli), at the time of consumption. Milk and probiotics had been produced or supplied by Granarolo s.p.a.
• Placebo milk
Ultra high temperature UHT, partly-skimmed milk (1% fat), highly digestible (lactose <0.01%) with standard proteins of milk (3.1%) and color additive "quantum satis". Milk had to be associated with a packet of maltodextrin "Food Grade", at the time of consumption. Milk and maltodextrin had been produced or supplied by Granarolo s.p.a.

Locations

Country	Name	City	State
Italy	University of Bologna-Department of Speciality, Diagnostic and Experimental Medicine	Bologna

Sponsors (1)

Lead Sponsor	Collaborator
University of Bologna

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Self reported quality of sleep	Sleep quality assessed by questionnaires	Change from baseline Sleep evaluation at 12 weeks milk intake
Primary	Measured quality of sleep	assessed by actigraph	Change from baseline Sleep evaluation at 12 weeks milk intake
Secondary	Levels of stress	Stress was evaluated by PSS questionnaire and 24-h urinary cortisol levels	12 weeks
Secondary	Inflammatory status	Dosage in plasma of the following cytokines: IL-1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-?, sCD40L, TNF-a, IL-17 A/F by Elisa immunoassay.	12 weeks
Secondary	Evalution of glycomics	Plasmatic N-glycans by capillary electrophoresis (DSA-FACE).	12 weeks
Secondary	Levels of anxiety	Stress was evaluated by STAI-Y2	12 weeks
Secondary	Levels of depression.	Stress was evaluated by BDI-II questionnaire	12 weeks
Secondary	Evalution of epigenetic	Epigenetic analysis of ELOVL2, FHL2, PENK genes by "Sequenom"	12 weeks
Secondary	Gut Microbiota composition	Analysis of gut-microbiota composition by 454 Pyrosequencing of the V4 region of the 16S rRNA gene.	12 weeks