D-serine + TMS for Depression

(PAT-DS Trial)

Overseen By Julia Tom, BS, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mclean Hospital

Must be taking: D-serine

Must not be taking: Drug-drug interactions

Disqualifiers: Renal disease, Seizure history, others

Compensation: Varies

Number of Visits: 33

Duration: 6 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining D-serine, a supplement, with transcranial magnetic stimulation (TMS) can improve outcomes for people with depression. Researchers seek to compare the effectiveness of D-serine plus TMS against TMS with a placebo pill. Individuals diagnosed with major depressive disorder who can swallow capsules may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes people taking medications with known drug-drug interactions. It's best to discuss your current medications with the trial team to see if they might interact with the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that D-serine is generally safe for humans. Studies have found that people tolerate it well, even in high doses. Researchers are also studying its potential benefits for conditions like schizophrenia and depression.

Transcranial Magnetic Stimulation (TMS) is considered safe and well-tolerated. It has been used successfully in various situations. When combined with other treatments, as in this study, TMS remains a safe option with no major safety concerns reported.

In summary, both D-serine and TMS have demonstrated good safety records in past studies, suggesting they are likely safe for humans, although individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about D-serine combined with Transcranial Magnetic Stimulation (TMS) for depression because it offers a unique approach compared to current treatments like SSRIs, SNRIs, and psychotherapy. Unlike these standard options, D-serine is an amino acid that may enhance the effectiveness of TMS by modulating the NMDA receptors in the brain, potentially leading to faster and more robust improvements in depressive symptoms. This combination targets brain function directly, which could offer a promising alternative for patients who have not found relief with traditional therapies.

What evidence suggests that this trial's treatments could be effective for depression?

In this trial, participants will receive either D-serine combined with Transcranial Magnetic Stimulation (TMS) or a placebo combined with TMS. Previous studies have shown that D-serine can improve symptoms of depression, particularly in individuals with severe major depressive disorder. This compound affects a part of the brain involved in mood regulation. TMS has also proven effective for depression, with about 50% of patients experiencing long-lasting relief. Researchers are exploring the combination of D-serine with TMS because D-serine might enhance the effects of TMS, potentially leading to better outcomes for those dealing with depression. Early evidence suggests this combination could offer a stronger treatment option. ^{1 2 4 6 7}

Who Is on the Research Team?

Kerry Ressler, MD, PhD

Principal Investigator

Mclean Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with a clinical diagnosis of Major Depressive Disorder (MDD) who speak English and can swallow capsules. Specific details on exclusion criteria are not provided, but typically include factors that could interfere with the study or patient safety.

Inclusion Criteria

I speak English.

I can swallow pills.

I may have conditions that could make certain treatments risky for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive 30 sessions of rTMS combined with either placebo or D-serine over 6 weeks

6 weeks

30 visits (in-person, daily Mon-Fri)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• D-serine
• TMS

Trial Overview The study tests if adding D-serine to repetitive Transcranial Magnetic Stimulation (rTMS), using iTBS and 18-Hz protocols, improves depression outcomes compared to rTMS with a placebo. The hypothesis suggests that D-serine may boost NMDA receptor function and enhance treatment effects.

How Is the Trial Designed?

Group I: D-serine Active Control 1 Intervention

D-serine + TMS

Group II: Placebo Placebo Group 1 Intervention

Placebo + TMS

Who Is Running the Clinical Trial?

Mclean Hospital

Lead Sponsor

Trials

221

Recruited

22,500+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06876129?locStr=United+States&country=United+States&aggFilters=status%3A

Pharmacologic Augmentation of TMS for Depression With ... The goal of this study is to test whether combining D-serine with 30 treatments of a) iTBS and b) 18-Hz protocols will enhance clinical outcomes compared to ...

2. trialx.com trialx.com/clinical-trials/listings/325523/pharmacologic-augmentation-of-tms-for-depression-with-d-serine/?&geo_lat=42.2945&geo_lng=-71.2992&radius=10&place=Wellesley&user_country=United%20States

Pharmacologic Augmentation of TMS for Depression With ... The goal of this study is to test whether combining D-serine with 30 treatments of a) iTBS and b) 18-Hz protocols will enhance clinical outcomes ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40436209/

Adjunctive d-serine treatment for major depressive disorder Subgroup analyses indicated that d-serine significantly improved depressive symptoms in participants with severe MDD, with a trend towards ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S3050529125001163

Transcranial Magnetic Stimulation At week 26, 16/32(50 %) showed sustained remission on HDRS-17 and BDI-II; relapse/retreatment had occurred in 25 % on HDRS-17 and 28.1 % on BDI-II. This ...

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2019.00025/full

D-Serine: Potential Therapeutic Agent and/or Biomarker in ... Relevant to both schizophrenia and depression, preclinical and clinical studies with D-serine indicate that it may be effective in reducing cognitive ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6372501/

D-Serine: Potential Therapeutic Agent and/or Biomarker in ... Relevant to both schizophrenia and depression, preclinical and clinical studies with D-serine indicate that it may be effective in reducing cognitive ...

7. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.726365/full

D-Serine: A Cross Species Review of Safety D-serine appears safe at currently studied maximal doses, with potential safety in combination with DAAO inhibitors.