Trial Outcomes & Findings for Acute Glycine Pharmacodynamic Study (NCT NCT01610011)

Results Overview

Brain and plasma glycine levels are measured with proton magnetic resonance spectroscopy at 4T and analytically, respectively. Because glycine doses were limited to 30 g to avoid nausea and vomiting, some subjects with higher weights were administered lower doses per body weight of glycine (g/kg). Therefore, we corrected MRS data by the actual glycine dose administered (g/kg) to account for dosing differences.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

21 participants

Primary outcome timeframe

For up to 2 hours

Results posted on

2015-10-27

Participant Flow

Participant milestones

Participant milestones
Measure	Glycine Administration Glycine will be administered once orally to all subjects to determine brain and plasma pharmacodynamics. Glycine administration: Glycine will be administered once as a 250 cc lemon-flavored beverage based on each subject's body weight. The drink concentration will be 0.4 g/kg glycine (not to exceed 30 grams). Subjects will have 10 minutes to consume the beverage.	Glycine Administration GLDC Mutation Subjects Glycine will be administered once orally to all subjects to determine brain and plasma pharmacodynamics. Glycine administration: Glycine will be administered once as a 250 cc lemon-flavored beverage based on each subject's body weight. The drink concentration will be 0.4 g/kg glycine (not to exceed 30 grams). Subjects will have 10 minutes to consume the beverage.
Overall Study STARTED	19	2
Overall Study COMPLETED	9	2
Overall Study NOT COMPLETED	10	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Acute Glycine Pharmacodynamic Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glycine Administration GLDC Subjects n=2 Participants Glycine will be administered once orally to all subjects to determine brain and plasma pharmacodynamics. Glycine administration: Glycine will be administered once as a 250 cc lemon-flavored beverage based on each subject's body weight. The drink concentration will be 0.4 g/kg glycine (not to exceed 30 grams). Subjects will have 10 minutes to consume the beverage.	Total n=11 Participants Total of all reporting groups	Glycine Administration n=9 Participants Glycine will be administered once orally to all subjects to determine brain and plasma pharmacodynamics. Glycine administration: Glycine will be administered once as a 250 cc lemon-flavored beverage based on each subject's body weight. The drink concentration will be 0.4 g/kg glycine (not to exceed 30 grams). Subjects will have 10 minutes to consume the beverage.
Age, Continuous	48 years STANDARD_DEVIATION 19.8 • n=4 Participants	35.9 years STANDARD_DEVIATION 13.4 • n=27 Participants	33.2 years STANDARD_DEVIATION 11.5 • n=93 Participants
Sex: Female, Male Female	1 Participants n=4 Participants	2 Participants n=27 Participants	1 Participants n=93 Participants
Sex: Female, Male Male	1 Participants n=4 Participants	9 Participants n=27 Participants	8 Participants n=93 Participants

PRIMARY outcome

Timeframe: For up to 2 hours

Population: Subjects completing the magnetic resonance spectroscopy study.

Brain and plasma glycine levels are measured with proton magnetic resonance spectroscopy at 4T and analytically, respectively. Because glycine doses were limited to 30 g to avoid nausea and vomiting, some subjects with higher weights were administered lower doses per body weight of glycine (g/kg). Therefore, we corrected MRS data by the actual glycine dose administered (g/kg) to account for dosing differences.

Outcome measures

Outcome measures
Measure	Glycine Administration Controls n=9 Peak dose-normalized glycine increase Glycine will be administered once orally to all subjects to determine brain and plasma pharmacodynamics. Glycine administration: Glycine will be administered once as a 250 cc lemon-flavored beverage based on each subject's body weight. The drink concentration will be 0.4 g/kg glycine (not to exceed 30 grams). Subjects will have 10 minutes to consume the beverage.	Glycine Administration GLDC Mutation Subjects n=2 Peak dose-normalized glycine increase Glycine will be administered once orally to all subjects to determine brain and plasma pharmacodynamics. Glycine administration: Glycine will be administered once as a 250 cc lemon-flavored beverage based on each subject's body weight. The drink concentration will be 0.4 g/kg glycine (not to exceed 30 grams). Subjects will have 10 minutes to consume the beverage.
Brain Glycine Increments After Oral Glycine Administration Measured With MRS as Glycine/Total Creatine, Normalized to the Glycine Dose Administered (g/kg).	393 Percent brain glycine/creatine increase Standard Error 50	677 Percent brain glycine/creatine increase Standard Error 117

Adverse Events

Glycine Administration Controls

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Glycine Administration GLDC Mutation Subjects

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Glycine Administration Controls n=11 participants at risk Glycine will be administered once orally to all subjects to determine brain and plasma pharmacodynamics. Glycine administration: Glycine will be administered once as a 250 cc lemon-flavored beverage based on each subject's body weight. The drink concentration will be 0.4 g/kg glycine (not to exceed 30 grams). Subjects will have 10 minutes to consume the beverage.	Glycine Administration GLDC Mutation Subjects n=2 participants at risk Glycine will be administered once orally to all subjects to determine brain and plasma pharmacodynamics. Glycine administration: Glycine will be administered once as a 250 cc lemon-flavored beverage based on each subject's body weight. The drink concentration will be 0.4 g/kg glycine (not to exceed 30 grams). Subjects will have 10 minutes to consume the beverage.
Gastrointestinal disorders Any adverse event	0.00% 0/11	0.00% 0/2

Additional Information

Marc J. Kaufman, Ph.D., Principal Investigator

McLean Hospital

Phone: 617-855-3469

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place