Nutritional Trial With Probiotic Fortified Milk in Women Affected by Insomnia (Prosit)

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

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.

Study Overview

• Status: Completed
• Conditions: Sleep Disorders
• Intervention / Treatment: Dietary supplement: Fortified milk; Dietary supplement: Placebo milk

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40126
    • University of Bologna-Department of Speciality, Diagnostic and Experimental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fortified milk; The subjects assumed daily 250 ml of fortified milk for 12 weeks.	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.; Other Names: golden milk
PLACEBO_COMPARATOR: Placebo milk; The subjects assumed daily 250 ml of placebo milk for 12 weeks.	Dietary supplement: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self reported quality of sleep	Sleep quality assessed by questionnaires	Change from baseline Sleep evaluation at 12 weeks milk intake
Measured quality of sleep	assessed by actigraph	Change from baseline Sleep evaluation at 12 weeks milk intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of stress	Stress was evaluated by PSS questionnaire and 24-h urinary cortisol levels	12 weeks
Inflammatory status	Dosage in plasma of the following cytokines: IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40L, TNF-α, IL-17 A/F by Elisa immunoassay.	12 weeks
Evalution of glycomics	Plasmatic N-glycans by capillary electrophoresis (DSA-FACE).	12 weeks
Levels of anxiety	Stress was evaluated by STAI-Y2	12 weeks
Levels of depression.	Stress was evaluated by BDI-II questionnaire	12 weeks
Evalution of epigenetic	Epigenetic analysis of ELOVL2, FHL2, PENK genes by "Sequenom"	12 weeks
Gut Microbiota composition	Analysis of gut-microbiota composition by 454 Pyrosequencing of the V4 region of the 16S rRNA gene.	12 weeks

Collaborators and Investigators

• Sponsor: University of Bologna

Study record dates

Study Major Dates

• Study Start: November 20, 2015
• Primary Completion (ACTUAL): July 1, 2016
• Study Completion (ACTUAL): August 31, 2017

Study Registration Dates

• First Submitted: July 22, 2016
• First Submitted That Met QC Criteria: June 12, 2019
• First Posted (ACTUAL): June 13, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 13, 2019
• Last Update Submitted That Met QC Criteria: June 12, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: golden milk, insomnia, gut-brain axis
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Sleep Wake Disorders
• Other Study ID Numbers: MIUR prot.n.257/Ric.

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO