Magnesium Sulfate Versus 5% Dextrose With Treatment Resistant Depression

A Double-blinded Randomized Study of IV Infusion of Magnesium Sulfate Versus 5% Dextrose in a Crossover Design in Male and Female Volunteers With Treatment Resistant Depression

The proposed study is a 1-week, randomized, double-blind, placebo-controlled, trial to evaluate the efficacy of an IV infusion of magnesium sulfate on symptoms of treatment resistant mild and moderate depression in 20 males and females (21-70 years of age). Participants will be assessed at screening/baseline, day 1, day 2, day 7, and day 8. Each subject will be randomized in a double-blind fashion to receive either IV infusion of magnesium sulfate or 5% dextrose followed by a washout period of 5 days then crossover to receive either IV infusion of 5% dextrose or magnesium sulfate.

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Dietary supplement: Magnesium sulfate

Detailed Description

Purpose:

1. To determine the magnesium deficient status in treatment-resistant mild and moderate depression patients via 24-hour urine magnesium assessment before and after IV magnesium infusion.
2. Correlation of intracellular magnesium (EXATEST), urine magnesium, and serum magnesium as well as sensitivity to the IV magnesium infusion.
3. To assess the effectiveness of magnesium sulfate infusion on treatment resistant mild and moderate depression patients.

Objectives:

Primary:

1. To investigate the magnesium deficient status in treatment-resistant mild and moderate depression patients via assay of 24-hour urine magnesium, blood magnesium, and EXATEST of intracellular magnesium of epithelial cells before and after IV infusion.
2. To assess the effectiveness of the magnesium sulfate infusion on the mean change in scores on the Hamilton Rating Scale for Depression and the Patient Health Questionnaire (PHQ-9) for depression.

Secondary:

1. To correlate the levels of magnesium with the scores on the Hamilton Rating Scale for Depression and the Patient Health Questionnaire (PHQ-9) for depression.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Clinical Research Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Potential participants must be English speaking.
2. Between the ages of 21 and 70.
3. Overall healthy and have no difficulty with digestion or absorption of food
4. Have treatment-resistant depression defined as failure of clinical improvement after 6 weeks with an approved dose of a Selective Serotonin Uptake Inhibitor (SSRI), Serotonin-Norepinephrine Reuptake Inhibitor (SNRI), Selective Noradrenaline Reuptake Inhibitor (NRI), tricyclic antidepressant, or bupropion.
5. Willing to provide informed consent to participate in the study.
6. Willing and able to comply with all study procedures and data recording obligations for the entire length of the study.
7. Able and willing to abstain from alcohol from 48 hours prior to the first intravenous infusion until after completion of the post-treatment follow-up visit (Day 2) and from 48 hours prior to the second intravenous infusion until after completion of the post-treatment follow-up visit (Day 8).
8. If currently taking an SSRI for more than 90 days, have maintained the same dose for the past 90 days.
9. A non-smoker or have quit smoking at least 6 months ago.

Exclusion Criteria:

1. Currently enrolled (or have been in the last 30 days) in another research trial for investigative nutritional or other therapies thought to have an impact on depression.
2. Currently taking a medication or nutritional supplement containing more than 100% RDA of magnesium (for women over age 31, it is 320 mg/day and for men over age 31, it is 420 mg/day) and unable to discontinue using it 14 days prior to the Day 1 visit. (Current use must be stopped 2 weeks before enrolling in the study and during trial.)
3. Diagnosed with any medical condition, including diabetes, cardiovascular disease, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric (except for depression), immunologic, hematologic, gastrointestinal, or metabolic disease requiring medical treatment that would preclude participation in the study.
4. Taking Digoxin (used to treat congestive heart failure and to slow the heart rate in patients with atrial fibrillation.
5. Taking penicillamine (also known as Cuprimine or Depen for Wilson's disease or rheumatoid arthritis).
6. Taking any antibiotic (including tetracycline or a quinolone).
7. Taking any psychotropic medication for any indication, except sedatives for sleep such as Zolpidem, in addition to the SSRI, SNRI, NRI, tricyclic antidepressant, or bupropion in the course of treatment for your depression.
8. Taking a SSRI, SNRI, NRI, tricyclic antidepressant, or bupropion for less than 90 days or unable to maintain the same therapeutic regimen throughout the study duration.
9. A history of any medical or surgical procedure that would preclude participation in the study.
10. Diagnosed with gastrointestinal disorders that could lead to uncertain resorption of the study supplements.
11. Pregnant, plan to become pregnant, or currently breast feeding.
12. Unwilling to avoid pregnancy (use medically-acceptable birth control method during the study with at least one method for the period of one month prior to beginning of the study until at least three months after study completion or are surgically sterile or postmenopausal (at least 12 months without a period).
13. Systolic blood pressure >160 mmHg or diastolic blood pressure >90 mmHg.
14. Had any of the following abnormal laboratory test values: (a) bilirubin > 2x upper normal limit, (b) AST and ALT > 2x upper normal limit, (c) serum creatinine > 1.5 mg/dl, (d) blood glucose below 80 mg/dl or above 110 mg/dl, (e) calcium level < 8.6 mg/dl, or (f) triglycerides >200 mg/dl.
15. Currently undergoing any chemotherapy or radiation treatment for cancer, have an active malignancy, or have had within the past 5 years any type of malignancy, other than non-melanomatous skin malignancies.
16. A history of substance abuse (e.g., alcohol, opiates, benzodiazepines, or amphetamines).
17. Currently consume more than 6 standard alcoholic drinks a week (A standard alcoholic drink is defined as one bottle/can of beer, one glass of wine, or one ounce of hard liquor.).
18. Diagnosed with a terminal illness.
19. Donated blood in the last 30 days.
20. Any severe, acute illness within the last five days.
21. Have a pacemaker or internal medical device.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Magnesium sulfate crossover; IV infusion of magnesium sulfate followed by 5-day washout period and crossover to 5% dextrose (placebo)	Dietary supplement: Magnesium sulfate; 4 grams magnesium sulfate in 100 ml IV over 4 hours
PLACEBO_COMPARATOR: Placebo crossover; IV infusion of 5% dextrose with 5 day washout and crossover to magnesium sulfate	Dietary supplement: Magnesium sulfate; 4 grams magnesium sulfate in 100 ml IV over 4 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnesium levels in treatment resistant mild and moderate depression	To investigate the magnesium deficient status in treatment-resistant mild and moderate depression patients via assay of 24-hour urine magnesium, blood magnesium, and EXATEST of intracellular magnesium of epithelial cells before and after IV infusion.	8 days
Self reported depression measures	To assess the effectiveness of the magnesium sulfate infusion on the mean change in scores on the Hamilton Rating Scale for Depression and the Patient Health Questionnaire (PHQ-9) for depression.	8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of magnesium levels with self reported measures of depression	To correlate the levels of magnesium with the scores on the Hamilton Rating Scale for Depression and the Patient Health Questionnaire (PHQ-9) for depression	8 days

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: Life Extension Foundation Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: May 9, 2012
• First Submitted That Met QC Criteria: May 10, 2012
• First Posted (ESTIMATE): May 11, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 21, 2016
• Last Update Submitted That Met QC Criteria: January 19, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: magnesium sulfate; mild moderate treatment-resistant depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate
• Other Study ID Numbers: 20110168