Condition category
Nutritional, Metabolic, Endocrine
Date applied
04/04/2017
Date assigned
28/04/2017
Last edited
28/04/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The vegetarian diet, or the stricter vegan diet, requires particular attention to any deficiency (shortage) in certain nutrients. In particular, vitamin B12 is present exclusively in animal products and is involved in many important reactions in the body. Vegans that exclude animal products from their diet may incur in a deficient nutritional status. The deficiency in the long term may lead to the onset of anemia (low blood iron) and neurological problems (issues with the brain, spine and nerves), as well as effects on the immune system (ability to fight off illness), hyperhomocysteinemia (an elevation of an amino acid in the blood that is linked to heart disease) and cognitive (mental) decline. In a situation where you people are unable to get enough B12 it is normal take supplements such as tablets that contain the nutrient. The aim of this study is to investigate the effect of the consumption of two different dosages (a high dose and a low dose) of vitamin B12 supplement sublingual tablets (a tablet that is inserted beneath the tongue to dissolve) in people with a marginal (low) deficiency.

Who can participate?
Vegan and vegetarian healthy adults aged 20-60 years old with a vitamin B12 deficiency.

What does the study involve?
Participants undergo a medical examination and complete questionnaires to determine eligibility. They are then randomly allocated to one of two groups. Those in the first group receive a low dose (350mcg/week) of a B12 dietary supplement (a tablet) that they take daily for three months. Those in the second group receive a high dose (2000mcg/week) of a vitamin B12 dietary supplement (a tablet) that they take weekly for three months (they take placebo pills the other six days of the week). Participants are followed up with blood samples before the study and at day 15, 30, 60 and 90 to monitor their nutritional levels and assess the concentration of the vitamin in their blood.

What are the possible benefits and risks of participating?
Participants may benefit from the expected improvement of vitamin B12 nutritional status. There is a slight risk of temporary headaches, balance problems or vision disorders associated with high dose supplements.

Where is the study run from?
University of Milano Department of Food, Environmental and Nutritional Sciences (Italy)

When is the study starting and how long is it expected to run for?
March 2015 to April 2017

Who is funding the study?
Phoenix SRL (Italy)

Who is the main contact?
1. Professor Salvatore Ciappellano (Scientific)
salvatore.ciappellano@unimi.it
2. Dr Antonella Brusamolino (Scientific)

Trial website

Contact information

Type

Scientific

Primary contact

Prof Salvatore Ciappellano

ORCID ID

http://orcid.org/0000-0002-2468-9557

Contact details

University of Milan
Department of Food
Environmental and Nutritional Sciences
Division of Human Nutrition
Via G. Celoria 2
Milan
20133
Italy
+39 02 503 16725
salvatore.ciappellano@unimi.it

Type

Scientific

Additional contact

Dr Antonella Brusamolino

ORCID ID

Contact details

University of Milan
Department of Food
Environmental and Nutritional Sciences
Division of Human Nutrition
Via G. Celoria 2
Milan
20133
Italy

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

11/15 University of Milano - ethical comitee

Study information

Scientific title

Evaluation of nutritional status of vitamin B12 in vegans and vegetarians with marginal deficiency after 12 weeks of supplementation with two dosages of a sublingual formulation

Acronym

NuCbl

Study hypothesis

Dietary supplementation with low dose of vitamin B12 sublingually administered to vegan subjects should allow the recovery of an adequate nutritional status related to vitamin B12.

Ethics approval

Ethics Committee of the University of Milan, 04/03/2015, ref: 11/15

Study design

12 week two armed dietary interventional randomised parallel trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Community

Trial type

Quality of life

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Healthy volunteers with B12 marginal deficiency

Intervention

Participants are enrolled in the study after they complete a specific questionnaire and medical examination to determine eligibility. Participants are then randomly allocated to one of two groups based on when they joined the study.

Control group (Hd- high dose): Participants are given a high vitamin B12 concentration (2000mcg/week) dietary supplement that they take weekly for three months. Supplements are given tablets that dissolve under the tongue. Participants in this group take tablets everyday but only once a week take a pill that is enriched with B12, the other six days the tablets are placebo.

Test group (Ld- low dose): Participants are given a low vitamin B12 concentration (350mcg/week) dietary supplement that they take daily for three months. Supplements are given as tablets that dissolve under the tongue and are taken daily.

Fasting blood samples (about 30 mL) are obtained from all participants, at baseline and after 15, 30, 60 and 90 days to assess Vitamin B12, holotranscobalamine, metilmalonic acid, homocysteine, folic acid, vitamin B6 and complete blood count. This is also done to monitor the modification of the nutritional status during the entire intervention.

Intervention type

Supplement

Phase

Drug names

Primary outcome measures

Nutritional status (vitamin B12, holotranscobalamin, methylmalonic and homocysteine concentrations) are measured using blood samples at baseline, day 15, day 30, day 60 and day 90

Secondary outcome measures

1. Complete blood count is measured using blood samples at baseline, day 15, day 30, day 60 and day 90
2. Serum levels of folic acid is measured using blood samples at baseline, day 15, day 30, day 60 and day 90
3. Vitamin B6 is measured using blood samples at baseline, day 15, day 30, day 60 and day 90

Overall trial start date

12/02/2014

Overall trial end date

10/04/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Healthy men/women (20-60 years of age)
2. Moderate smoking (about 5-6 cigarette/day)
3. Moderate physical activity (25-30 min per day of brisk walk or jog)
4. Moderate alcohol consumption (up to 14 drinks per week)
5. Plasma levels of vitamin B12 lower than 220 pmol / L
6. Follow a vegan diet
7. No regular intake of drugs (for any type of disease)
8. Non allergic subjects

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

At least 40 subjects

Participant exclusion criteria

1. History of cardiovascular, coronary, diabetes, hepatic, renal, or gastrointestinal diseases.
2. Use of any drugs, medications at least one month before the beginning of the experiment.
3. Use of vitamin B12 supplements at least one year before the beginning of the experiment.
4. Omnivore subjects

Recruitment start date

05/05/2015

Recruitment end date

04/12/2016

Locations

Countries of recruitment

Italy

Trial participating centre

University of Milan
Department of Food, Environmental and Nutritional Sciences Via Celoria 2
Milano
20133
Italy

Sponsor information

Organisation

Phoenix S.R.L. - LongLife Nutritional Supplements

Sponsor details

Dr.ssa Licia Colombo
Sig. Giuseppe Galliani
Via 2 Giugno
60/A1
Peschiera Borromeo
20068
Italy
+39 02 5165531
l.colombo@pho.it

Sponsor type

Industry

Website

www.longlife.it

Funders

Funder type

University/education

Funder name

University of Milan

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Phoenix S.R.L. - LongLife Nutritional Supplements

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal. Expected participation in conferences and public events to present the results.

IPD sharing plan:
The datasets generated during and/or analysed during the current study are/will be available upon request from Salvatore Ciappellano salvatore.ciappellano@unimi.it

Intention to publish date

31/12/2017

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes