NCT02179788

Brief Summary

Most new mothers in the United States will start off breastfeeding. For some mothers, despite following best practices, they are not able to meet their breastfeeding goals due to unexplained low milk supply. At the same time, nearly 1 in 4 new mothers are pre-diabetic (elevated blood sugar, but not yet diabetic). My progression of research suggests that the same metabolic factors causing pre-diabetes may also be causing low milk supply. Metformin is a widely prescribed drug to treat high blood sugar. This study is a preliminary, small scale randomized trial designed to test for a trend in the hypothesis that metformin is safe and potentially effective in treating low milk supply in insulin resistant and pre-diabetic mothers.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jun 2014

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

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

June 1, 2014

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

June 30, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 2, 2014

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2016

Completed
4.3 years until next milestone

Results Posted

Study results publicly available

October 19, 2020

Completed
Last Updated

October 19, 2020

Status Verified

September 1, 2016

Enrollment Period

2.1 years

First QC Date

June 30, 2014

Results QC Date

September 9, 2020

Last Update Submit

October 13, 2020

Conditions

Keywords

lactationbreastfeedinghuman milkinsulinmetforminprediabetespre-diabetesinsulin resistance

Outcome Measures

Primary Outcomes (1)

  • Peak Change in Milk Output

    Maximal change in maternal breast milk production (g/24 hours) between baseline and 4 weeks post-intervention in a model adjusted for baseline milk volume, maternal day postpartum of randomization, and baseline fasting plasma glucose.

    baseline and 4 weeks post-intervention

Study Arms (2)

Standard care plus metformin

EXPERIMENTAL

67% of stage 2 eligible mothers will be randomly allocated to this arm. Mothers will be instructed to thoroughly empty their breasts at least 8 times per day and to take the assigned study drug.

Behavioral: Standard careDrug: Metformin

Standard Care plus placebo

PLACEBO COMPARATOR

33% of Stage 2 eligible mothers will be randomly allocated to this arm. Mothers will be instructed to thoroughly empty their breasts at least 8 times per day (Standard Care) and to take the assigned study drug. The placebo arm will be consuming methylcellulose USP Powder encapsulated in #00 opaque capsules (supplied by PCCA, Houston TX) for 4 weeks according to the following schedule: * Days 1-7, take 1 capsule with evening meal * Days 8-14, take 3 capsules with evening meal * Days 14-28 (or through completion of post-intervention data collection), take four capsules with evening meal Actual increase in dose may occur more slowly if standard titration schedule is not well tolerated. Adjustments to schedule will be made in consultation with the adult medicine study co-investigator.

Behavioral: Standard careDrug: Placebo

Interventions

Standard careBEHAVIORAL

Mothers will be instructed to thoroughly empty their breasts at least 8 times per 24 hours by breastfeeding, followed by breast expression with a combination of hand -expression and the use of a hospital-grade electric breast pump (provided by study).

Also known as: Breast expression
Standard Care plus placeboStandard care plus metformin

The metformin arm will be consuming Glucophage XR (metformin hydrochloride extended release, 750 or 500 mg, encapsulated in #00 opaque capsules for 4 weeks according to the following schedule: * Days 1-7, take one 750 mg capsule with evening meal (750 mg/day) * Days 8-14, take three 500 mg capsule with evening meal (1500 mg/day) * Days 14-28 (or through completion of post-intervention data collection), take four 500 mg capsules with evening meal (2000 mg/day) Actual increase in dose may occur more slowly if standard titration schedule is not well tolerated. Adjustments to schedule will be made in consultation with the adult medicine study co-investigator. The trial duration is 28 days (with a +/- 3 day cushion)

Also known as: Glucophage
Standard care plus metformin

The placebo arm will be consuming methylcellulose USP Powder encapsulated in #00 opaque capsules (supplied by PCCA, Houston TX) for 4 weeks according to the following schedule: * Days 1-7, take 1 capsule with evening meal * Days 8-14, take 3 capsules with evening meal * Days 14-28 (or through completion of post-intervention data collection), take four capsules with evening meal Actual increase in dose may occur more slowly if standard titration schedule is not well tolerated. Adjustments to schedule will be made in consultation with the adult medicine study co-investigator.

Also known as: methylcellulose
Standard Care plus placebo

Eligibility Criteria

Age20 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Stage 1 Criteria (for participation in baseline measurement phase):
  • identified with low milk supply by a Cincinnati-area IBCLC
  • mother denies obvious cause of low milk supply such as pituitary disorder, breast surgery, severe lack of breast emptying (\< 4 times per day), or failure to show any signs of lactogenesis
  • mother at least 20 years of age
  • infant is between 1 week and 2 calendar months old
  • mother gave birth to a single, healthy, term (\>37 weeks gestation) infant
  • mother free of breast and nipple infections
  • mother lives within study catchment area
  • mother has not been diagnosed with Type 1 or Type 2 Diabetes Mellitus
  • mother willing to sustain consistent use of herbal galactogogues (such as fenugreek) during follow up measurements (2-4 weeks) as was consumed during the baseline measurements
  • mother not currently taking a prescription medication that may affect the hormones of lactation and not planning to initiate any such drug for at least the next 2-4 weeks.
  • mother has established pediatric care for the infant
  • successful completion of baseline measurements (involving 24-hour test weighing of milk output and undergoing baseline measurements at the clinical research center, including providing fasting blood samples)
  • body mass index is \>19.0 kg/m2 (i.e., not underweight)
  • evidence of likely insulin resistance, based on at least one of the following: mean fasting plasma glucose between 95.0 - 125.0 g/dL, inclusive; abdominal obesity; history of polycystic ovary syndrome; or history of gestational diabetes
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Related Publications (5)

  • Nommsen-Rivers LA, Chantry CJ, Peerson JM, Cohen RJ, Dewey KG. Delayed onset of lactogenesis among first-time mothers is related to maternal obesity and factors associated with ineffective breastfeeding. Am J Clin Nutr. 2010 Sep;92(3):574-84. doi: 10.3945/ajcn.2010.29192. Epub 2010 Jun 23.

    PMID: 20573792BACKGROUND
  • Nommsen-Rivers LA, Dolan LM, Huang B. Timing of stage II lactogenesis is predicted by antenatal metabolic health in a cohort of primiparas. Breastfeed Med. 2012 Feb;7(1):43-9. doi: 10.1089/bfm.2011.0007. Epub 2011 Apr 27.

    PMID: 21524193BACKGROUND
  • Lemay DG, Ballard OA, Hughes MA, Morrow AL, Horseman ND, Nommsen-Rivers LA. RNA sequencing of the human milk fat layer transcriptome reveals distinct gene expression profiles at three stages of lactation. PLoS One. 2013 Jul 5;8(7):e67531. doi: 10.1371/journal.pone.0067531. Print 2013.

    PMID: 23861770BACKGROUND
  • Wagner EA, Chantry CJ, Dewey KG, Nommsen-Rivers LA. Breastfeeding concerns at 3 and 7 days postpartum and feeding status at 2 months. Pediatrics. 2013 Oct;132(4):e865-75. doi: 10.1542/peds.2013-0724. Epub 2013 Sep 23.

    PMID: 24062375BACKGROUND
  • Nommsen-Rivers L, Thompson A, Riddle S, Ward L, Wagner E, King E. Feasibility and Acceptability of Metformin to Augment Low Milk Supply: A Pilot Randomized Controlled Trial. J Hum Lact. 2019 May;35(2):261-271. doi: 10.1177/0890334418819465. Epub 2019 Jan 10.

Related Links

MeSH Terms

Conditions

Glucose IntoleranceInsulin ResistanceBreast FeedingPrediabetic State

Interventions

Standard of CareMetforminMethylcellulose

Condition Hierarchy (Ancestors)

HyperglycemiaGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesHyperinsulinismFeeding BehaviorBehaviorDiabetes MellitusEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health CareQuality of Health CareHealth Services AdministrationHealth Care Quality, Access, and EvaluationBiguanidesGuanidinesAmidinesOrganic ChemicalsCelluloseGlucansPolysaccharidesCarbohydrates

Limitations and Caveats

Many mothers wanted to delay enrollment until they could trial non-pharmacologic methods. Many mothers were hesitant to use a medication to try to increase milk supply once seeing how low baseline supply was.

Results Point of Contact

Title
Dr. Laurie Nommsen-Rivers
Organization
University of Cincinnati

Study Officials

  • Laurie A Nommsen-Rivers, PhD

    Children's Hospital Medical Center, Cincinnati

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 30, 2014

First Posted

July 2, 2014

Study Start

June 1, 2014

Primary Completion

July 1, 2016

Study Completion

July 1, 2016

Last Updated

October 19, 2020

Results First Posted

October 19, 2020

Record last verified: 2016-09

Locations