Evaluation of Efficacy and Safety of add-on Sarcosine in Patients With Major Depressive Disorder

NCT04975100 | Completed Phase 4

• 1 other identifier: IEC/AIIMSBBSR/PGThesis/21/07
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

One-third of the patients with major depressive disorder do not respond to conventional antidepressants that act through the mono-aminergic system. The available treatment modalities, including SSRIs, are slow to act and have a lag time before showing improvement in symptoms of patients. To overcome these treatment hurdles, add-on therapy to standard antidepressant drugs may lead to better therapeutic outcomes. Sarcosine, which is a nutraceutical, modulates glutamate neurotransmission has an ameliorative effect on the disease symptoms of depression and negative symptoms of schizophrenia. The only clinical study done on depressive patients by Huang et al. cannot be generalized due to certain inherent limitations. To date, there is no randomized controlled trial with add-on sarcosine to current antidepressant therapy to the best of our knowledge. So, we considered sarcosine can be the candidate drug for add-on therapy due to its multiple mechanisms on the glutaminergic system. Adding sarcosine to ongoing antidepressant therapy may either increase their response rate or decrease adverse drug reactions by decreasing the dose requirement or may show a quicker therapeutic effect. Hence, the present randomized controlled trial has been planned to evaluate the efficacy and safety of sarcosine as add-on therapy in major depressive disorder.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change in severity of depressive symptoms from baseline.

  The change in symptoms of depression will be evaluated using Montgomery Asberg Depression Rating Scale score. Each item of the questionnaire yields a score of 0 to 6. The overall score ranges from 0 to 60. A higher score indicates more severe depression.

  8 weeks

Secondary Outcomes (7)

• Response rate

  8 weeks

• Remission rate

  8 weeks

• Severity of symptoms

  Baseline

• Change in severity of symptoms

  8 weeks

• Change in serum Brain Derived Neurotrophic Factor (BDNF) from baseline

  8 weeks

Study Arms (2)

Test

EXPERIMENTAL

Patients in the test group will get Sarcosine 500 mg capsules once daily as an add-on to ongoing SSRI treatment.

Drug: Sarcosine and SSRI

Control

ACTIVE COMPARATOR

Patients in the control group will get identical-looking capsules containing placebo in addition to SSRI at an once daily dose

Drug: Placebo and SSRI

Interventions

Sarcosine and SSRI DRUG

Patients in the test group will get Sarcosine 500 mg capsules once daily as an add-on to ongoing SSRI treatment

Test

Placebo and SSRI DRUG

Patients in the control group will get identical-looking capsules containing placebo in addition to SSRI at an once daily dose

Control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18-65 years, of either gender with the clinical diagnosis of major depressive disorder (DSM 5).
• Patients with MADRS score ≥ 7 and ≤ 34 (Mild to moderate severity).
• Patients who are on a stable dose of Sertraline 50 mg or any other SSRI (selective serotonin reuptake inhibitor) therapy in equivalent dose.
• Patients who have given informed written consent.

You may not qualify if:

• Major depressive patient treated with Electro Convulsive Therapy recently.
• History of epilepsy, head trauma, or other major neurological or medical disorders.
• Patients with a history of bipolar depression.
• Patients with schizophrenia or other psychotic disorder.
• Patients with suicidal risk.
• Patients with cognitive impairment.
• Initiating or stopping formal psychotherapy within six weeks before enrolment.
• Patients with comorbidities like any malignancies, hepatic, renal, cardiovascular, neurological or endocrinal, respiratory dysfunction.
• Substance abuse history of psychoactive agents.
• Pregnant and lactating mothers.

Sponsors & Collaborators

• All India Institute of Medical Sciences, Bhubaneswar: lead

Study Sites (1)

AIIMS

Bhubaneswar, Odisha, 751019, India

Location

Related Publications (15)

• Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. doi: 10.1001/jama.289.23.3095.

  PMID: 12813115 RESULT

• Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005 Jun;62(6):593-602. doi: 10.1001/archpsyc.62.6.593.

  PMID: 15939837 RESULT

• Hawton K, van Heeringen K. Suicide. Lancet. 2009 Apr 18;373(9672):1372-81. doi: 10.1016/S0140-6736(09)60372-X.

  PMID: 19376453 RESULT

• Hasler G. Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry. 2010 Oct;9(3):155-61. doi: 10.1002/j.2051-5545.2010.tb00298.x.

  PMID: 20975857 RESULT

• Ruhe HG, Mason NS, Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry. 2007 Apr;12(4):331-59. doi: 10.1038/sj.mp.4001949. Epub 2007 Jan 16.

  PMID: 17389902 RESULT

• Perez-Caballero L, Torres-Sanchez S, Romero-Lopez-Alberca C, Gonzalez-Saiz F, Mico JA, Berrocoso E. Monoaminergic system and depression. Cell Tissue Res. 2019 Jul;377(1):107-113. doi: 10.1007/s00441-018-2978-8. Epub 2019 Jan 10.

  PMID: 30627806 RESULT

• Pochwat B, Nowak G, Szewczyk B. An update on NMDA antagonists in depression. Expert Rev Neurother. 2019 Nov;19(11):1055-1067. doi: 10.1080/14737175.2019.1643237. Epub 2019 Jul 22.

  PMID: 31328587 RESULT

• Phillips C. Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection. Neural Plast. 2017;2017:7260130. doi: 10.1155/2017/7260130. Epub 2017 Aug 8.

  PMID: 28928987 RESULT

• Lee MY, Lin YR, Tu YS, Tseng YJ, Chan MH, Chen HH. Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials. J Biomed Sci. 2017 Feb 28;24(1):18. doi: 10.1186/s12929-016-0314-8.

  PMID: 28245819 RESULT

• Peyrovian B, Rosenblat JD, Pan Z, Iacobucci M, Brietzke E, McIntyre RS. The glycine site of NMDA receptors: A target for cognitive enhancement in psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jun 8;92:387-404. doi: 10.1016/j.pnpbp.2019.02.001. Epub 2019 Feb 6.

  PMID: 30738126 RESULT

• Chen KT, Wu CH, Tsai MH, Wu YC, Jou MJ, Huang CC, Wei IH. Antidepressant-like effects of long-term sarcosine treatment in rats with or without chronic unpredictable stress. Behav Brain Res. 2017 Jan 1;316:1-10. doi: 10.1016/j.bbr.2016.06.004. Epub 2016 Aug 21.

  PMID: 27555541 RESULT

• Huang CC, Wei IH, Huang CL, Chen KT, Tsai MH, Tsai P, Tun R, Huang KH, Chang YC, Lane HY, Tsai GE. Inhibition of glycine transporter-I as a novel mechanism for the treatment of depression. Biol Psychiatry. 2013 Nov 15;74(10):734-41. doi: 10.1016/j.biopsych.2013.02.020. Epub 2013 Apr 3.

  PMID: 23562005 RESULT

• Commons KG, Linnros SE. Delayed Antidepressant Efficacy and the Desensitization Hypothesis. ACS Chem Neurosci. 2019 Jul 17;10(7):3048-3052. doi: 10.1021/acschemneuro.8b00698. Epub 2019 Mar 11.

  PMID: 30807103 RESULT

• Chen KT, Tsai MH, Wu CH, Jou MJ, Wei IH, Huang CC. AMPA Receptor-mTOR Activation is Required for the Antidepressant-Like Effects of Sarcosine during the Forced Swim Test in Rats: Insertion of AMPA Receptor may Play a Role. Front Behav Neurosci. 2015 Jun 18;9:162. doi: 10.3389/fnbeh.2015.00162. eCollection 2015.

  PMID: 26150775 RESULT

• Padhan M, Mohapatra D, Mishra BR, Maiti R, Jena M. Efficacy and safety of add-on sarcosine in patients with major depressive disorder: A randomized controlled trial. J Psychiatr Res. 2024 Oct;178:298-304. doi: 10.1016/j.jpsychires.2024.08.026. Epub 2024 Aug 22.

  PMID: 39180989 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Sarcosine; Selective Serotonin Reuptake Inhibitors

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

N-substituted Glycines; Glycine; Amino Acids; Amino Acids, Peptides, and Proteins; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs

Study Officials

• Rituparna Maiti, MD

  AIIMS, Bhubaneswar

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The recruited patients will be randomized by block randomization into two treatment groups using computer-generated random codes with an allocation of 1:1. The random allocation code of the participants will be generated by the investigator who will not be involved in patient recruitment. For allocation concealment, sequentially numbered, identical-looking drug dispensing containers will be used.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 14, 2021
• First Posted: July 23, 2021
• Study Start: August 26, 2021
• Primary Completion: April 30, 2023
• Study Completion: April 30, 2023
• Last Updated: July 25, 2023

Record last verified: 2023-07

Locations

IN (1)