Trial Outcomes & Findings for Creatine Augmentation for Adolescent Females With Treatment-Resistant Major Depressive Disorder (NCT NCT02134808)

Last Updated: 2024-07-03

Results Overview

PCr will be measured through phosphorus magnetic resonance spectroscopy (31P-MRS). This will be performed in a 3 Tesla magnetic resonance imaging (MRI) scanner. Creatine concentration before and after treatment. By convention, 31P MRS data are typically reported as metabolite ratios.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

71 participants

Primary outcome timeframe

Baseline and 8 weeks

Results posted on

2024-07-03

Participant Flow

Participant milestones

Participant milestones
Measure	Creatine 28 Subjects randomized to this study arm will receive 10 grams of creatine daily for 8 weeks. Creatine: Creatine is a nutritional supplement.	Placebo 23 Subjects randomized to this study arm will receive 10 grams of placebo daily for 8 weeks. Placebo: The placebo is an inactive ingredient similar in appearance, weight and density to the active treatment.	Healthy Comparison 20 Subjects seen for screening and baseline scan. No randomization or treatment intervention for subjects enrolled as a Healthy Comparison.
Overall Study STARTED	28	23	20
Overall Study COMPLETED	24	19	20
Overall Study NOT COMPLETED	4	4	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Creatine Augmentation for Adolescent Females With Treatment-Resistant Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Creatine n=28 Participants 28 Subjects randomized to this study arm will receive 10 grams of creatine daily for 8 weeks. Creatine: Creatine is a nutritional supplement.	Placebo n=23 Participants 23 Subjects randomized to this study arm will receive 10 grams of placebo daily for 8 weeks. Placebo: The placebo is an inactive ingredient similar in appearance, weight and density to the active treatment.	Healthy Comparison n=20 Participants 20 Subjects seen for screening and baseline scan. No randomization or treatment intervention for subjects enrolled as a Healthy Comparison.	Total n=71 Participants Total of all reporting groups
Age, Categorical <=18 years	14 Participants n=5 Participants	9 Participants n=7 Participants	7 Participants n=5 Participants	30 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants	14 Participants n=7 Participants	13 Participants n=5 Participants	41 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	17.6 years STANDARD_DEVIATION 2.2 • n=5 Participants	17.8 years STANDARD_DEVIATION 2.0 • n=7 Participants	17.4 years STANDARD_DEVIATION 3.2 • n=5 Participants	17.6 years STANDARD_DEVIATION 2.4 • n=4 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	23 Participants n=7 Participants	20 Participants n=5 Participants	71 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White Non-Hispanic	27 Participants n=5 Participants	19 Participants n=7 Participants	16 Participants n=5 Participants	62 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	28 participants n=5 Participants	23 participants n=7 Participants	20 participants n=5 Participants	71 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 8 weeks

Outcome measures

Outcome measures
Measure	Creatine n=28 Participants 28 Subjects randomized to this study arm will receive 10 grams of creatine daily for 8 weeks.	Placebo n=23 Participants 23 Subjects randomized to this study arm will receive 10 grams of placebo daily for 8 weeks.	Healthy Comparison n=20 Participants 20 Subjects seen for screening and baseline scan. No randomization or treatment intervention for subjects enrolled as a Healthy Comparison.
Brain Phosphocreatine (PCr) Concentrations Baseline	.1812802 Ratio Standard Deviation .011512	.1796093 Ratio Standard Deviation .0070168	.1850427 Ratio Standard Deviation .0059435
Brain Phosphocreatine (PCr) Concentrations Week 8	.1876206 Ratio Standard Deviation .0121833	.181464 Ratio Standard Deviation .008267	NA Ratio Standard Deviation NA Healthy Comparison participants were only scanned at baseline.

SECONDARY outcome

Timeframe: 8 weeks

The Children's Depression Rating Scale-Revised (CDRS-R) and Montgomery-Asberg Depression Rating Scale (MADRS) will be administered to understand the severity of depressive symptoms, and how these symptoms change throughout the course of the study. The CDRS-R has a range of minimum score 17 and maximum score 113, with higher scores indicating more severe depression. The MADRS has a range of 0 to 60 with higher scores indicating more severe depressive symptoms.

Outcome measures

Outcome measures
Measure	Creatine n=28 Participants 28 Subjects randomized to this study arm will receive 10 grams of creatine daily for 8 weeks.	Placebo n=23 Participants 23 Subjects randomized to this study arm will receive 10 grams of placebo daily for 8 weeks.	Healthy Comparison n=20 Participants 20 Subjects seen for screening and baseline scan. No randomization or treatment intervention for subjects enrolled as a Healthy Comparison.
Children's Depression Rating Scale-Revised (CDRS-R); Montgomery-Asberg Depression Rating Scale (MADRS) CDRS-R Baseline	58.28571 score on a scale Standard Deviation 6.980699	60.3913 score on a scale Standard Deviation 6.719978	21.9 score on a scale Standard Deviation 2.425739
Children's Depression Rating Scale-Revised (CDRS-R); Montgomery-Asberg Depression Rating Scale (MADRS) CDRS-R Week 8	41.95833 score on a scale Standard Deviation 12.47773	44.15789 score on a scale Standard Deviation 10.25921	NA score on a scale Standard Deviation NA Healthy Comparison participants were only assessed at baseline.
Children's Depression Rating Scale-Revised (CDRS-R); Montgomery-Asberg Depression Rating Scale (MADRS) MADRS Baseline	28.71428 score on a scale Standard Deviation 5.394491	31.47826 score on a scale Standard Deviation 4.832368	2.315789 score on a scale Standard Deviation 2.029029
Children's Depression Rating Scale-Revised (CDRS-R); Montgomery-Asberg Depression Rating Scale (MADRS) MADRS Week 8	16.16667 score on a scale Standard Deviation 11.21981	18.73684 score on a scale Standard Deviation 11.29819	NA score on a scale Standard Deviation NA Healthy Comparison participants were only assessed at baseline.

Adverse Events

Creatine

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Creatine n=28 participants at risk Subjects randomized to this study arm will receive 10 grams of creatine daily for 8 weeks. Creatine: Creatine is a nutritional supplement.	Placebo n=23 participants at risk Subjects randomized to this study arm will receive 10 grams of placebo daily for 8 weeks. Placebo: The placebo is an inactive ingredient similar in appearance, weight and density to the active treatment.
Psychiatric disorders Suicidal Ideation/Behavior	3.6% 1/28 • Number of events 1 • Adverse events were collected from participants at every visit, starting after the treatment intervention was dispensed at baseline. Adverse events were assessed up to 8 weeks. Healthy comparison participants were only seen for a baseline scan. Healthy comparison participants were not exposed to any treatment intervention, therefore, adverse events were not collected.	0.00% 0/23 • Adverse events were collected from participants at every visit, starting after the treatment intervention was dispensed at baseline. Adverse events were assessed up to 8 weeks. Healthy comparison participants were only seen for a baseline scan. Healthy comparison participants were not exposed to any treatment intervention, therefore, adverse events were not collected.

Other adverse events

Other adverse events
Measure	Creatine n=28 participants at risk Subjects randomized to this study arm will receive 10 grams of creatine daily for 8 weeks. Creatine: Creatine is a nutritional supplement.	Placebo n=23 participants at risk Subjects randomized to this study arm will receive 10 grams of placebo daily for 8 weeks. Placebo: The placebo is an inactive ingredient similar in appearance, weight and density to the active treatment.
Gastrointestinal disorders Abdominal cramp, Nausea, Indigestion, Diarrhea	53.6% 15/28 • Number of events 35 • Adverse events were collected from participants at every visit, starting after the treatment intervention was dispensed at baseline. Adverse events were assessed up to 8 weeks. Healthy comparison participants were only seen for a baseline scan. Healthy comparison participants were not exposed to any treatment intervention, therefore, adverse events were not collected.	52.2% 12/23 • Number of events 26 • Adverse events were collected from participants at every visit, starting after the treatment intervention was dispensed at baseline. Adverse events were assessed up to 8 weeks. Healthy comparison participants were only seen for a baseline scan. Healthy comparison participants were not exposed to any treatment intervention, therefore, adverse events were not collected.
Nervous system disorders Headache	64.3% 18/28 • Number of events 35 • Adverse events were collected from participants at every visit, starting after the treatment intervention was dispensed at baseline. Adverse events were assessed up to 8 weeks. Healthy comparison participants were only seen for a baseline scan. Healthy comparison participants were not exposed to any treatment intervention, therefore, adverse events were not collected.	65.2% 15/23 • Number of events 37 • Adverse events were collected from participants at every visit, starting after the treatment intervention was dispensed at baseline. Adverse events were assessed up to 8 weeks. Healthy comparison participants were only seen for a baseline scan. Healthy comparison participants were not exposed to any treatment intervention, therefore, adverse events were not collected.
Respiratory, thoracic and mediastinal disorders Respiratory	35.7% 10/28 • Number of events 11 • Adverse events were collected from participants at every visit, starting after the treatment intervention was dispensed at baseline. Adverse events were assessed up to 8 weeks. Healthy comparison participants were only seen for a baseline scan. Healthy comparison participants were not exposed to any treatment intervention, therefore, adverse events were not collected.	60.9% 14/23 • Number of events 17 • Adverse events were collected from participants at every visit, starting after the treatment intervention was dispensed at baseline. Adverse events were assessed up to 8 weeks. Healthy comparison participants were only seen for a baseline scan. Healthy comparison participants were not exposed to any treatment intervention, therefore, adverse events were not collected.

Additional Information

Dr. Douglas Kondo

University of Utah

Phone: (801) 587-1549

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place