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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03985228
Recruitment Status : Completed
First Posted : June 13, 2019
Last Update Posted : June 13, 2019
Information provided by (Responsible Party):
Claudio Franceschi, University of Bologna

Brief 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.

Condition or disease Intervention/treatment Phase
Sleep Disorders Dietary Supplement: Fortified milk Dietary Supplement: Placebo milk Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Promotion of Consumer's Health: Nutritional Enhancement/Valorization of Agrofood Italian Traditional Products (PROS.IT)
Study Start Date : November 20, 2015
Actual Primary Completion Date : July 2016
Actual Study Completion Date : August 31, 2017

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 Name: 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.

Primary Outcome Measures :
  1. Self reported quality of sleep [ Time Frame: Change from baseline Sleep evaluation at 12 weeks milk intake ]
    Sleep quality assessed by questionnaires

  2. Measured quality of sleep [ Time Frame: Change from baseline Sleep evaluation at 12 weeks milk intake ]
    assessed by actigraph

Secondary Outcome Measures :
  1. Levels of stress [ Time Frame: 12 weeks ]
    Stress was evaluated by PSS questionnaire and 24-h urinary cortisol levels

  2. Inflammatory status [ Time Frame: 12 weeks ]
    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.

  3. Evalution of glycomics [ Time Frame: 12 weeks ]
    Plasmatic N-glycans by capillary electrophoresis (DSA-FACE).

  4. Levels of anxiety [ Time Frame: 12 weeks ]
    Stress was evaluated by STAI-Y2

  5. Levels of depression. [ Time Frame: 12 weeks ]
    Stress was evaluated by BDI-II questionnaire

  6. Evalution of epigenetic [ Time Frame: 12 weeks ]
    Epigenetic analysis of ELOVL2, FHL2, PENK genes by "Sequenom"

  7. Gut Microbiota composition [ Time Frame: 12 weeks ]
    Analysis of gut-microbiota composition by 454 Pyrosequencing of the V4 region of the 16S rRNA gene.

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03985228

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University of Bologna-Department of Speciality, Diagnostic and Experimental Medicine
Bologna, Italy, 40126
Sponsors and Collaborators
University of Bologna
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Principal Investigator: Claudio Franceschi, MD University of Bologna
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Responsible Party: Claudio Franceschi, Professor emeritus, University of Bologna Identifier: NCT03985228    
Other Study ID Numbers: MIUR prot.n.257/Ric.
First Posted: June 13, 2019    Key Record Dates
Last Update Posted: June 13, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Claudio Franceschi, University of Bologna:
golden milk, insomnia, gut-brain axis
Additional relevant MeSH terms:
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Sleep Wake Disorders
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Mental Disorders