Efficacy and Safety of Magnesium Vitamin B6 in First Episode Bipolar Disorder

Sponsor

Mclean Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05837104

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled proof-of-concept clinical trial to assess the efficacy and safety of Magnesium-vitamin B6in combination with treatment as usual for treating symptoms of depression, stress, and anxiety in patients with first episode bipolar I disorder.

Condition or Disease	Intervention/Treatment	Phase
Bipolar I Disorder Depression, Anxiety Stress	Drug: Magnesium vitamin B6 Drug: Placebo	Phase 2

Detailed Description

After a first episode of bipolar disorder, subsequent depressive and anxiety symptoms can pose a major challenge to an individual's recovery early in the illness. Individuals often have depressive and anxiety symptoms for a significant proportion of their time. These mood and anxiety symptoms are associated with higher risk for relapse, chronicity and disability. Previous studies have shown that the combination of Magnesium-vitamin B6 has beneficial effects on stress, and depressive and anxiety symptoms. This randomized, double-blind, placebo-controlled trial will assess the benefits of Magnesium-vitamin B6 in combination with treatment as usual (standard of clinical care) on depressive and anxiety symptoms and stress in individuals with bipolar disorder in the early phase of illness. In addition, we aim to assess the effects of Magnesium-vitamin B6 on brain free [Mg2+] and energy metabolism, observed to be altered in bipolar disorder, measured by in vivo 31P magnetic resonance spectroscopy (31P MRS). Magnesium is a promising targeted intervention for bipolar disorder given its significant effects on energy metabolism.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled Clinical Trial to Assess the Efficacy and Safety of Magnesium Vitamin B6 in Combination With Treatment as Usual in First Episode of Bipolar I Disorder

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

May 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Magnesium vitamin B6 Magnesium vitamin B6 (MagnéVie B6®) composed of Magnesium citrate (100mg) and Pyridoxine hydrochloride (10mg) in tablet form, taken three times daily for four weeks.	Drug: Magnesium vitamin B6 Magnesium citrate (100mg) and Pyridoxine hydrochloride (10mg) in tablet form, taken three times daily for four weeks. Other Names: MagnéVie B6®
Placebo Comparator: Placebo Placebo tablet will be taken three times daily for four weeks.	Drug: Placebo Placebo tablet, three times daily for four weeks.

Arm

Intervention/Treatment

Experimental: Magnesium vitamin B6

Magnesium vitamin B6 (MagnéVie B6®) composed of Magnesium citrate (100mg) and Pyridoxine hydrochloride (10mg) in tablet form, taken three times daily for four weeks.

Drug: Magnesium vitamin B6

Magnesium citrate (100mg) and Pyridoxine hydrochloride (10mg) in tablet form, taken three times daily for four weeks.

Other Names:

MagnéVie B6®

Placebo Comparator: Placebo

Placebo tablet will be taken three times daily for four weeks.

Drug: Placebo

Placebo tablet, three times daily for four weeks.

Outcome Measures

Primary Outcome Measures

Change in depressive symptoms [4 weeks]
Change from baseline to week 4 in Hamilton Rating Scale for Depression total score

Secondary Outcome Measures

Change in anxiety symptoms [4 weeks]
Change from baseline to week 4 in Hamilton Anxiety Rating Scale total score
Change in stress symptoms [4 weeks]
Change from baseline to week 4 in Depression Anxiety Stress Scales (DASS-42) Stress Subscale score
Change in CGI [4 weeks]
Change from baseline to week 4 in Clinical Global Impression Scale
Change in cognitive measure [4 weeks]
Change from baseline to week 4 in MATRICS Total score
Changes in brain energy metabolism markers [4 weeks]
Change from baseline to week 4 in brain energy metabolites and pH as measured by 31P magnetic resonance spectroscopy
Change in brain Mg2+ concentration [4 weeks]
Change from baseline to week 4 in Mg2+ concentration as measured by 31P MRS
Change in adverse events. [4 weeks]
Change from baseline to week 4 in adverse events.events

Other Outcome Measures

Change in WHODAS [4 weeks]
Change from baseline to week 4 in WHODAS scale
Change in WHO QOL [4 weeks]
Change from baseline to week 4 in WHO QOL scale
Change in Mg blood level [4 weeks]
Change from baseline to week 4 in Mg blood levels

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Persons between the ages of 18 and 45
DSM V diagnosis of bipolar I disorder, onset of illness in the last 7 years
Minimum of two of the following symptoms on the Hamilton Rating Scale of Depression HAM-D (HAM-D, 17 item): depressed mood, feelings of guilt, anxiety-psychic, anxiety-somatic, somatic symptoms-general, somatic symptoms-gastrointestinal; with HAM-D total scores of 15 or lower.
Moderate to extremely severe stress at screening, defined as a DASS-42 stress subscale score of >18
Young Mania Rating Scale (YMRS) scores of less than 15
Ability to sign informed consent.
Stable disorder and no change in psychiatric medications within 2 weeks of screening and expected to not require addition of any new psychiatric medications during the duration of the 4 weeks of the study.

Exclusion Criteria:

Unable to sign informed consent.
Persons weighing over 350lbs.
Declines to participate.
Bipolar NOS, Cyclothymia, or Schizoaffective Bipolar type.
2 or more manic symptoms that meet DSM-V criteria.
Persons currently taking antidepressants.
Persons of childbearing potential who are not using a medically accepted means of contraception.
Persons who are deemed a serious suicide or homicide risk.
Unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
The following DSM-V diagnoses: 1) substance use disorders, including alcohol, active within 2 months; 2) schizophrenia; 3) delusional disorder; 4) psychotic disorders not otherwise specified; 5) schizoaffective disorder; 6) acute bereavement; 7) severe borderline or antisocial personality disorder.
Persons meeting criteria for bipolar mixed episode.
Exposure to levodopa, quinidine, and proton-pump inhibitors within 3 months prior to screening.
Severe hypomagnesemia (serum magnesium of 0.45 mmol/L).
Persons who have taken an investigational psychotropic drug within the past 6 months unless the investigational drug was a one-time dose.
Seizure disorder.
Dietary supplements including SAMe, St. John's Wort, DHEA, Inositol, and Ginko biloba.
Previous treatment with the following procedures: vagus nerve stimulation, or deep brain stimulation.
Have a history of electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the last 3 months.
Have any medical condition that would prevent blood draws.
Have a history of significant head injury.
Individuals with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases)
Individuals with allergies to magnesium citrate anhydrous, pyridoxine hydrochloride or any of the other components of Magne B6