NCT04245826

Brief Summary

We propose to conduct a systematic literature review and meta-analysis to assess the association of low-calorie sweetened beverages (LCSBs) on cardiometabolic outcomes in prospective cohort studies. We will be using methodological approaches (change in LCSBs intake, and/or substitution analysis) that attempt to overcome the issue of reverse causality associated with studies of LCSBs and cardiometabolic disease. Ten cardiometabolic outcomes will be assessed:

  1. 1.Global adiposity - body weight
  2. 2.Global adiposity - BMI
  3. 3.Global adiposity - body fat
  4. 4.Abdominal adiposity - waist circumference
  5. 5.Overweight/obesity incidence
  6. 6.Metabolic syndrome incidence
  7. 7.Type 2 diabetes incidence
  8. 8.Cardiovascular disease incidence
  9. 9.Cardiovascular disease mortality
  10. 10.Total mortality

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started May 2019

Shorter than P25 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 16, 2019

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

January 23, 2020

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 29, 2020

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2020

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2020

Completed
Last Updated

February 25, 2020

Status Verified

February 1, 2020

Enrollment Period

10 months

First QC Date

January 23, 2020

Last Update Submit

February 21, 2020

Conditions

Keywords

body weightBMIwaist circumferencediabetescardiovascular diseasemetabolic syndromemortalityoverweight incidenceobesity incdience

Outcome Measures

Primary Outcomes (10)

  • Global measures of adiposity with established clinical relevance - body weight

    Change in body weight

    More than 1 year

  • Global measures of adiposity with established clinical relevance - BMI

    Change in body mass index (BMI)

    More than 1 year

  • Global measures of adiposity with established clinical relevance - body fat

    Change in body fat

    More than 1 year

  • Abdominal measures of adiposity with established clinical relevance - waist circumference

    Change in waist circumference

    More than 1 year

  • Overweight/obesity incidence

    Risk ratio of Overweight/obesity incidence

    More than 1 year

  • Metabolic syndrome incidence

    Risk ratio of metabolic syndrome incidence

    More than 1 year

  • Type 2 diabetes incidence

    Risk ratio of type 2 diabetes incidence

    More than 1 year

  • Cardiovascular disease incidence

    Risk ratio of cardiovascular disease incidence

    More than 1 year

  • Cardiovascular disease mortality

    Risk ratio of Cardiovascular disease mortality

    More than 1 year

  • Total mortality

    Risk ratio of total mortality

    More than 1 year

Study Arms (1)

Low-calorie Sweetened Beverages (LCSBs)

Beverages exclusively using zero-energy (e.g., acesulfame-potassium, aspartame, cyclamate, saccharin, sucralose, advantame, neotame), and /or reduced-energy food additives (e.g., stevia, monk fruit).

Other: Change in LCSBs IntakeOther: Substitute LCSBs for SSBs or Water

Interventions

Effect of changing LCSBs intake

Low-calorie Sweetened Beverages (LCSBs)

Effect of substituting LCSBs for SSBs or Water

Low-calorie Sweetened Beverages (LCSBs)

Eligibility Criteria

Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Varies

You may qualify if:

  • Prospective cohorts studies
  • Duration: more than 1 year follow-up
  • Exposure: LCSBs
  • Change analysis or substitution analysis of exposure

You may not qualify if:

  • Non-human studies
  • Less than 1 year follow-up
  • Analysis of baseline or prevalent intake of exposure only

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital

Toronto, Ontario, M5C 2T2, Canada

Location

Related Publications (8)

  • Khan TA, Malik VS, Sievenpiper JL. Letter by Khan et al Regarding Article, "Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women's Health Initiative". Stroke. 2019 Jun;50(6):e167-e168. doi: 10.1161/STROKEAHA.119.025571. Epub 2019 May 16. No abstract available.

    PMID: 31092156BACKGROUND
  • Malik VS. Non-sugar sweeteners and health. BMJ. 2019 Jan 3;364:k5005. doi: 10.1136/bmj.k5005. No abstract available.

    PMID: 30606710BACKGROUND
  • Johnson RK, Lichtenstein AH, Anderson CAM, Carson JA, Despres JP, Hu FB, Kris-Etherton PM, Otten JJ, Towfighi A, Wylie-Rosett J; American Heart Association Nutrition Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Quality of Care and Outcomes Research; and Stroke Council. Low-Calorie Sweetened Beverages and Cardiometabolic Health: A Science Advisory From the American Heart Association. Circulation. 2018 Aug 28;138(9):e126-e140. doi: 10.1161/CIR.0000000000000569.

    PMID: 30354445BACKGROUND
  • Toews I, Lohner S, Kullenberg de Gaudry D, Sommer H, Meerpohl JJ. Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies. BMJ. 2019 Jan 2;364:k4718. doi: 10.1136/bmj.k4718.

    PMID: 30602577BACKGROUND
  • Azad MB, Abou-Setta AM, Chauhan BF, Rabbani R, Lys J, Copstein L, Mann A, Jeyaraman MM, Reid AE, Fiander M, MacKay DS, McGavock J, Wicklow B, Zarychanski R. Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ. 2017 Jul 17;189(28):E929-E939. doi: 10.1503/cmaj.161390.

    PMID: 28716847BACKGROUND
  • Imamura F, Fretts A, Marklund M, Ardisson Korat AV, Yang WS, Lankinen M, Qureshi W, Helmer C, Chen TA, Wong K, Bassett JK, Murphy R, Tintle N, Yu CI, Brouwer IA, Chien KL, Frazier-Wood AC, Del Gobbo LC, Djousse L, Geleijnse JM, Giles GG, de Goede J, Gudnason V, Harris WS, Hodge A, Hu F; InterAct Consortium; Koulman A, Laakso M, Lind L, Lin HJ, McKnight B, Rajaobelina K, Riserus U, Robinson JG, Samieri C, Siscovick DS, Soedamah-Muthu SS, Sotoodehnia N, Sun Q, Tsai MY, Uusitupa M, Wagenknecht LE, Wareham NJ, Wu JH, Micha R, Forouhi NG, Lemaitre RN, Mozaffarian D; Fatty Acids and Outcomes Research Consortium (FORCE). Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies. PLoS Med. 2018 Oct 10;15(10):e1002670. doi: 10.1371/journal.pmed.1002670. eCollection 2018 Oct.

    PMID: 30303968BACKGROUND
  • Rogers PJ, Hogenkamp PS, de Graaf C, Higgs S, Lluch A, Ness AR, Penfold C, Perry R, Putz P, Yeomans MR, Mela DJ. Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. Int J Obes (Lond). 2016 Mar;40(3):381-94. doi: 10.1038/ijo.2015.177. Epub 2015 Sep 14.

    PMID: 26365102BACKGROUND
  • Lee JJ, Khan TA, McGlynn N, Malik VS, Hill JO, Leiter LA, Jeppesen PB, Rahelic D, Kahleova H, Salas-Salvado J, Kendall CWC, Sievenpiper JL. Relation of Change or Substitution of Low- and No-Calorie Sweetened Beverages With Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Prospective Cohort Studies. Diabetes Care. 2022 Aug 1;45(8):1917-1930. doi: 10.2337/dc21-2130.

MeSH Terms

Conditions

ObesityMetabolic SyndromeDiabetes Mellitus, Type 2Cardiovascular DiseasesBody WeightDiabetes Mellitus

Interventions

Water

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsInsulin ResistanceHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

HydroxidesAlkaliesInorganic ChemicalsAnionsIonsElectrolytesOxidesOxygen Compounds

Study Officials

  • John L Sievenpiper, MD,PhD,FRCPC

    University of Toronto

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

January 23, 2020

First Posted

January 29, 2020

Study Start

May 16, 2019

Primary Completion

March 1, 2020

Study Completion

May 1, 2020

Last Updated

February 25, 2020

Record last verified: 2020-02

Locations