Creatine as a Treatment Option for Depression in Methamphetamine Using Females

• Sponsor: Perry Renshaw (Other)
• Overall Status: Completed
• CT.gov ID: NCT01514630
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arm: 1
• Duration (Months): 25
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Methamphetamine (MA) is a psychostimulant drug with high abuse potential. MA can be smoked, snorted, injected or ingested orally to produce a release of high levels of dopamine into the brain and reduction of dopamine uptake. Its use results in feelings of pleasure, increased energy, and greater alertness lasting up to 12 hours. In 2010, the National Survey on Drug Use and Health reported that 353,000 Americans aged 12 or older reported being current MA users. Over the past decade MA use rates have fluctuated with current use rates on the decline; however, importantly, even though overall use rates are declining, use rates among males and females are approaching equal proportions. This use rate pattern is unlike other drugs of abuse, which typically demonstrate males using more than females. In some states, more females than males consider MA as their drug of choice. Namely, in a 2010 report in the state of Utah, more females were diagnosed with MA as a primary substance of abuse than males upon admission to treatment.

Depression and MA use are highly comorbid. The relationship between MA use and depression is likely bidirectional, with MA use causing changes in mood and being used as a self-medicating behavior to reduce symptoms of depression. Several studies have shown that depression rates are higher in MA-using females compared to their male counterparts. It is likely that neurobiological and psychosocial mechanisms contribute to increased incidence of depressive symptoms in females.

No clear treatment model exists to suggest how the comorbidity of depression and MA use is best managed. In studies of antidepressants for treatment of MA withdrawal and dependence, findings have suggested that antidepressants are ineffective for treating depressive symptoms.

Creatine is an organic acid occurring naturally in vertebrates, where it takes part in energy homeostasis in tissues with fluctuating energy demands. Exogenous creatine has been shown to increase brain concentrations of PCr. Neuroimaging studies of creatine have shown increased brain phosphocreatine (PCr) content with creatine administration. Therefore, we hypothesize that oral creatine administration will increase PCr levels and reduce depressive symptoms in a sample of depressed female MA users. This hypothesis will be tested by a within subjects design by giving depressed MA using females oral creatine for eight weeks and measuring PCr pre- and post-treatment with magnetic resonance spectroscopy. Moreover, depressive symptoms will be measured by administration of the Hamilton Depression Rating Scale twice weekly during the course of creatine treatment.

Condition or Disease	Intervention/Treatment	Phase
Depression; Substance Abuse; Substance Use; Neuroimaging; Dual Diagnosis	Drug: Creatine monohydrate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Creatine as a Treatment Option for Depression in Methamphetamine Using Females
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Creatine monohydrate 14 female depressed methamphetamine users received 5 grams of creatine monohydrate daily for eight weeks.	Drug: Creatine monohydrate; Five grams of creatine monohydrate will be administered for eight weeks.

Outcome Measures

Primary Outcome Measures

1. HAMD Rating Scores [Over the course of eight weeks. Depression rating scores will be measured weekly for eight weeks for each subject enrolled.]

   Eight weeks of oral creatine supplementation will result in improvements in Hamilton Depression Rating Scale (HAMD) in female methamphetamine users. HAMD scoring is based on 17 items. Minimum score is 0 and maximum 52. A score of 0-7 is considered to be normal. Scores of 20 or higher indicate moderate or severe depression. 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression ≥ 23 = Very Severe Depression

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 64 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Female gender, ages 18-64 years inclusive

2. Diagnosis of MA dependence or abuse within the past 12 months, with MA preferred drug of abuse, identified by the SCID-I-RV

3. Current diagnosis of Major Depressive Disorder identified by the SCID-I-RV

4. Current HAM-D17 score of > 15

Exclusion Criteria:

1. Diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder, identified by the SCID-I-RV

2. History of or current diagnosis of renal disease, such as chronic renal failure, acute renal failure or end stage renal disease

3. Diabetes type I or II

4. Colitis or diverticulitis

5. Seizure disorder

6. Current serious suicide risk identified by the Columbia Severity Suicide Rating Severity

7. Current treatment with an antipsychotic, mood stabilizer, or antidepressant

8. Positive HIV test

9. Active Hepatitis C

10. Contraindication to magnetic resonance scan

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Brain Institute of the University of Utah	Salt Lake City	Utah	United States	84108

Sponsors and Collaborators

• Perry Renshaw

Investigators

• Principal Investigator: Tracy Hellem, RN, The College of Nursing & Brain Institute, University of Utah
• Study Director: Perry Renshaw, MD, PhD, MBA, Department of Psychiatry, University of Utah

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Perry Renshaw, Professor of Psychiatry, University of Utah
• ClinicalTrials.gov Identifier: NCT01514630
• Other Study ID Numbers: 60398
• First Posted: Jan 23, 2012
• Last Update Posted: Jun 29, 2015
• Last Verified: Jun 1, 2015

• Additional relevant MeSH terms: Substance-Related Disorders; Depression; Depressive Disorder

Study Results

Participant Flow

Arm/Group Title	Creatine Monohydrate
Arm/Group Description	14 female depressed methamphetamine users received 5 grams of creatine monohydrate daily for eight weeks. Participants were seen twice weekly after creatine was initiated. All participants met SCID-I/P criteria for lifetime methamphetamine dependence or for current methamphetamine dependence. After consent was obtained, the principal investigator administered the SCID-I/P and HAMD, and if a female met SCID-I/P criteria and scored > 15 on the HAMD, the following additional screening data were collected: Beck Anxiety Inventory, C-SSRS , vital signs, concomitant medications, self-report drug use over the past 48 hours for cigarettes, alcohol, cocaine, methamphetamine, marijuana, heroin and prescription controlled substances, urine drug screen for methamphetamine, opiates, benzodiazepines, marijuana and cocaine, pregnancy testing and attendance in outpatient treatment and/or 12 step programs.
Period Title: Overall Study
STARTED	14
COMPLETED	11
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Creatine Monohydrate
Arm/Group Description	14 female depressed methamphetamine users will receive 5 grams of creatine monohydrate daily for eight weeks. Creatine monohydrate: Five grams of creatine monohydrate will be administered for eight weeks.
Overall Participants	14
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	14 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.4 (9.9)
Sex: Female, Male (Count of Participants)
Female	14 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	14 100%

Outcome Measures

1. Primary Outcome

Title	HAMD Rating Scores
Description	Eight weeks of oral creatine supplementation will result in improvements in Hamilton Depression Rating Scale (HAMD) in female methamphetamine users. HAMD scoring is based on 17 items. Minimum score is 0 and maximum 52. A score of 0-7 is considered to be normal. Scores of 20 or higher indicate moderate or severe depression. 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression ≥ 23 = Very Severe Depression
Time Frame	Over the course of eight weeks. Depression rating scores will be measured weekly for eight weeks for each subject enrolled.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Creatine Monohydrate
Arm/Group Description	14 female depressed methamphetamine users will receive 5 grams of creatine monohydrate daily for eight weeks. Creatine monohydrate: Five grams of creatine monohydrate will be administered for eight weeks.
Measure Participants	11
Baseline	16.86 (3.40)
week 2	10.71 (4.75)
week 3	9.81 (4.45)
week 4	7.33 (2.74)
week 5	8.35 (4.12)
week 6	7.73 (3.88)
week 7	6.28 (5.07)
week 8	7.36 (4.59)

Adverse Events

Arm/Group Title	Creatine Monohydrate
Arm/Group Description	14 female depressed methamphetamine users will receive 5 grams of creatine monohydrate daily for eight weeks. Creatine monohydrate: Five grams of creatine monohydrate will be administered for eight weeks.
All Cause Mortality
	Creatine Monohydrate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Creatine Monohydrate
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Other (Not Including Serious) Adverse Events
	Creatine Monohydrate
	Affected / at Risk (%)	# Events
Total	14/14 (100%)
Gastrointestinal disorders
Indigestion	1/14 (7.1%)
Diarrhea	4/14 (28.6%)
Stomach Discomfort	3/14 (21.4%)
General disorders
Cold and flu symptoms	10/14 (71.4%)
Polydipsia	1/14 (7.1%)
Headache	1/14 (7.1%)
Swelling in Hands	1/14 (7.1%)
Numbness and Tingling in hands	1/14 (7.1%)
Muscle Cramps	2/14 (14.3%)
Lightheaded	1/14 (7.1%)
Nausea	1/14 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.