Trial Outcomes & Findings for Metformin to Augment Low Milk Supply (MALMS) Study (NCT NCT02179788)

Last Updated: 2020-10-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

15 participants

Primary outcome timeframe

baseline and 4 weeks post-intervention

Results posted on

2020-10-19

Participant Flow

Participant milestones

Participant milestones
Measure	Standard Care Plus Metformin 10 stage 2 eligible mothers were randomly allocated to this arm. Mothers were instructed to thoroughly empty their breasts at least 8 times per day and to take the assigned study drug. Standard care: 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. 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, one 750 mg capsule with evening meal (750 mg/day) * Days 8-14, three 500 mg capsule with evening meal (1500 mg/day) * Days 14-28 (or through completion of post-intervention data collection),four 500 mg capsules with evening meal (2000 mg/day) The trial duration was28 days (with a +/- 3 day cushion)	Standard Care Plus Placebo 5 Stage 2 eligible mothers were randomly allocated to this arm. Mothers were instructed to thoroughly empty their breasts at least 8 times per day (Standard Care) and to take the assigned study drug. The placebo arm consumed methylcellulose USP Powder encapsulated in #00 opaque capsules 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 Standard care: Mothers were 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.
Overall Study STARTED	10	5
Overall Study COMPLETED	10	5
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Metformin to Augment Low Milk Supply (MALMS) Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard Care Plus Metformin n=10 Participants 10 stage 2 eligible mothers were randomly allocated to this arm. Mothers were instructed to thoroughly empty their breasts at least 8 times per day and to take the assigned study drug. Standard care: 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. 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, one 750 mg capsule with evening meal (750 mg/day) * Days 8-14, three 500 mg capsule with evening meal (1500 mg/day) * Days 14-28 (or through completion of post-intervention data collection),four 500 mg capsules with evening meal (2000 mg/day) The trial duration was28 days (with a +/- 3 day cushion)	Standard Care Plus Placebo n=5 Participants 5 Stage 2 eligible mothers were randomly allocated to this arm. Mothers were instructed to thoroughly empty their breasts at least 8 times per day (Standard Care) and to take the assigned study drug. The placebo arm consumed methylcellulose USP Powder encapsulated in #00 opaque capsules 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 Standard care: Mothers were 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.	Total n=15 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	33 years n=5 Participants	35 years n=7 Participants	34 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	5 participants n=7 Participants	15 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and 4 weeks post-intervention

Outcome measures

Outcome measures
Measure	Standard Care Plus Metformin n=10 Participants 10 stage 2 eligible mothers were randomly allocated to this arm. Mothers were instructed to thoroughly empty their breasts at least 8 times per day and to take the assigned study drug. Standard care: 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. 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, one 750 mg capsule with evening meal (750 mg/day) * Days 8-14, three 500 mg capsule with evening meal (1500 mg/day) * Days 14-28 (or through completion of post-intervention data collection),four 500 mg capsules with evening meal (2000 mg/day) The trial duration was28 days (with a +/- 3 day cushion)	Standard Care Plus Placebo n=5 Participants 5 Stage 2 eligible mothers were randomly allocated to this arm. Mothers were instructed to thoroughly empty their breasts at least 8 times per day (Standard Care) and to take the assigned study drug. The placebo arm consumed methylcellulose USP Powder encapsulated in #00 opaque capsules 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 Standard care: Mothers were 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.
Peak Change in Milk Output	8 milliliters Interval -23.0 to 33.0	-58 milliliters Interval -62.0 to -1.0

Adverse Events

Standard Care Plus Metformin

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Standard Care Plus Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Standard Care Plus Metformin n=20 participants at risk 10 stage 2 eligible mothers were randomly allocated to this arm. Mothers were instructed to thoroughly empty their breasts at least 8 times per day and to take the assigned study drug. Standard care: 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. 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, one 750 mg capsule with evening meal (750 mg/day) * Days 8-14, three 500 mg capsule with evening meal (1500 mg/day) * Days 14-28 (or through completion of post-intervention data collection),four 500 mg capsules with evening meal (2000 mg/day) The trial duration was28 days (with a +/- 3 day cushion)	Standard Care Plus Placebo n=10 participants at risk 5 Stage 2 eligible mothers were randomly allocated to this arm. Mothers were instructed to thoroughly empty their breasts at least 8 times per day (Standard Care) and to take the assigned study drug. The placebo arm consumed methylcellulose USP Powder encapsulated in #00 opaque capsules 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 Standard care: Mothers were 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.
Gastrointestinal disorders Nausea, vomiting diarrhea-Mom	30.0% 6/20 • Number of events 6 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	30.0% 3/10 • Number of events 3 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Gastrointestinal disorders gas/bloating/cramping-mom	20.0% 4/20 • Number of events 4 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	0.00% 0/10 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Nervous system disorders Headache-mom	15.0% 3/20 • Number of events 3 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	0.00% 0/10 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Reproductive system and breast disorders Mom-Breast pain	0.00% 0/20 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	10.0% 1/10 • Number of events 1 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Gastrointestinal disorders gas/diarrhea/constipation/reflux-infant	25.0% 5/20 • Number of events 5 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	40.0% 4/10 • Number of events 4 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Gastrointestinal disorders insufficient weight gain-infant	5.0% 1/20 • Number of events 1 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	0.00% 0/10 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Respiratory, thoracic and mediastinal disorders Runny nose/cold-infant	10.0% 2/20 • Number of events 2 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	0.00% 0/10 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Nervous system disorders Irritable/other-infant	10.0% 2/20 • Number of events 2 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	10.0% 1/10 • Number of events 1 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Skin and subcutaneous tissue disorders Mom-pruritis	0.00% 0/20 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	10.0% 1/10 • Number of events 1 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Reproductive system and breast disorders mom-uterine cramping and pain	0.00% 0/20 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	10.0% 1/10 • Number of events 1 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Cardiac disorders mom-hyperlipidemia and hypertriglyceridemia	5.0% 1/20 • Number of events 1 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	0.00% 0/10 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Psychiatric disorders mom-emotional distress	5.0% 1/20 • Number of events 1 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	0.00% 0/10 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.
Infections and infestations Infant-fever	5.0% 1/20 • Number of events 1 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.	10.0% 1/10 • Number of events 1 • 4 weeks Adverse events potentially applied to both mother and infant, so participant number doubled.

Additional Information

Dr. Laurie Nommsen-Rivers

University of Cincinnati

Phone: 513-558-0461

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place