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

Stress Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05837104
• Other study ID #: 2022P001911
• Status: Recruiting
• Phase: Phase 2
• Start date: December 13, 2023
• Est. completion date: December 2025

Study information

• Verified date: March 2024
• Source: Mclean Hospital
• Contact: Kyle Cuklanz, B.S.
• Phone: 617-855-2637
• Email: kcuklanz[@]mclean.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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, the investigators 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.
• 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 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

Related Conditions & MeSH terms

• Bipolar Disorder
• Bipolar I Disorder
• Depression
• Depression, Anxiety
• Stress

Intervention

Drug:
• Magnesium vitamin B6
Magnesium citrate (100mg) and Pyridoxine hydrochloride (10mg) in tablet form, taken three times daily for four weeks.
• Placebo
Placebo tablet, three times daily for four weeks.

Locations

Country	Name	City	State
United States	McLean Hospital	Belmont	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Mclean Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in World Health Organization Disability Assessment Schedule (WHODAS) score	Change from baseline to week 4 in World Health Organization Disability Assessment Schedule (WHODAS) scale. Scores range from 0-144; a higher score indicates greater dysfunction and disability in major life domains.	4 weeks
Other	Change in World Health Organization Quality of Life (WHOQOL) score	Change from baseline to week 4 in World Health Organization Quality of Life (WHOQOL) scale. Scores range from 1-130; a lower score indicates lower perceived quality of life.	4 weeks
Other	Change in Mg blood level	Change from baseline to week 4 in Mg blood levels.	4 weeks
Other	Change is Positive and Negative Syndrome Scale (PANSS) total score	Change from baseline to week 4 in Positive and Negative Syndrome Scale (PANSS) total score. Scores range from 23-161; a higher score indicates a more severe illness.	4 weeks
Other	Change in Young Mania Rating Scale (YMRS) total score	Change from baseline to week 4 in Young Mania Rating Scale (YMRS) total score. Scores range from 0-60; a higher score indicates a more severe illness.	4 weeks
Other	Change in Extrapyramidal Symptom Rating Scale (ESRS) total score	Change from baseline to week 4 in Extrapyramidal Symptom Rating Scale (ESRS) total score. Scores range from 0-102; a higher score indicates more severe symptoms.	4 weeks
Other	Change in Pittsburgh Sleep Quality Index (PSQI) total score	Change from baseline to week 4 in Pittsburgh Sleep Quality Index (PSQI) total score. Scores range from 0-21; a higher score indicates worse sleep quality.	4 weeks
Other	Change in Global Functioning Scale - Social and Role (GFS) total score	Change from baseline to week 4 in Global Functioning Scale - Social and Role (GFS) total score. Scores range from 6-60; a lower score indicates worse social and role functioning.	4 weeks
Primary	Change in depressive symptoms	Change from baseline to week 4 in Hamilton Rating Scale for Depression (HAM-D) total score. Scores range from 0-52; a higher score indicates a higher level of depression.	4 weeks
Secondary	Change in anxiety symptoms	Change from baseline to week 4 in Hamilton Anxiety Rating Scale (HAM-A) total score. Scores range from 0-56; a higher score indicates a higher level of anxiety.	4 weeks
Secondary	Change in stress symptoms	Change from baseline to week 4 in Depression Anxiety Stress Scales (DASS-42) Stress Subscale score. Scores range from 0-42; a higher score indicates a higher level of stress.	4 weeks
Secondary	Change in Clinical Global Impression (CGI) Scale	Change from baseline to week 4 in Clinical Global Impression (CGI) Scale. Scores range from 1-7; a higher score indicates higher severity of illness.	4 weeks
Secondary	Change in cognitive measure	Change from baseline to week 4 in MATRICS Consensus Cognitive Battery (MCCB) Total score. Scores range from 0.00%-100.00%; a higher score indicates higher cognition.	4 weeks
Secondary	Changes in brain ATP	Changes in ATP concentration as measured by in vivo 31P magnetic resonance spectroscopy.	4 weeks
Secondary	Changes in brain PCr	Changes in Phosphocreatine (PCr) concentration as measured by in vivo 31P magnetic resonance spectroscopy.	4 weeks
Secondary	Changes in brain pH	Changes in pH as measured by in vivo 31P magnetic resonance spectroscopy.	4 weeks
Secondary	Changes in brain inorganic phosphate concentration	Changes in inorganic phosphate (Pi) concentration as measured by in vivo 31P magnetic resonance spectroscopy.	4 weeks
Secondary	Change in brain Mg2+ concentration	Change from baseline to week 4 in Mg2+ concentration as measured by 31P MRS.	4 weeks
Secondary	Change in adverse events	Change from baseline to week 4 in adverse events.	4 weeks