DepressionNCT00101452

Safety and Effectiveness of S-adenosyl-l-methionine (SAMe) for the Treatment of Major Depression

A study testing S-adenosyl-l-methionine and Escitalopram in people with Depression, run by Maurizio Fava, MD at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to determine the safety and effectiveness of s-adenosyl-l-methionine (SAMe) in treating major depression. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Depression
What is being tested?: S-adenosyl-l-methionine and Escitalopram
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 199 participants
Where: 2 sitesUnited States
Study dates: Apr 2005to Jun 2010
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Diagnosis of major depression
Score of 25 or higher on the Inventory of Depressive Symptomatology (IDS-C) scale
Score of higher than 2 on the Clinical Global Impression Improvement (CGI) scale
Willing to use acceptable methods of contraception

Who cannot join

Suicidal or homicidal
Unstable illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
Any of the following mental conditions: organic mental disorders; schizophrenia; delusional disorder; psychotic disorders; bipolar disorder; recent bereavement; severe borderline or antisocial personality disorder; panic disorder; or obsessive compulsive disorder
Substance abuse, including alcohol abuse, within 6 months prior to study entry
Uncontrolled seizure disorder, or a seizure disorder controlled with psychotropic anticonvulsants
Psychotic features

Show all 16Show fewer

Current use of other psychotropic drugs
Hypothyroidism
Have taken 6 weeks or more of either escitalopram or SAMe during the current depressive episode
Previous intolerance of SAMe or escitalopram
Investigational psychotropic drugs within 1 year prior to study entry
Have received two or more antidepressant therapies of adequate doses and duration and failed to respond
Have received depression-focused psychotherapy
Bleeding tissue disorder, low platelet counts, a history of GI bleeding, or use of medications that alter bleeding risk
Long-term aspirin use
Pregnancy

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Massachusetts General Hospital
Boston, Massachusetts, 02114
Butler Hospital
Providence, Rhode Island, 02906

Other trials in United States

About this study

Official title: A Double-Blind, Placebo-Controlled Study of the Alternative Therapy S-Adenosyl-L-Methionine (SAMe) vs Escitalopram in Major Depressive Disorder (MDD)

The purpose of this study is to determine the safety and effectiveness of s-adenosyl-l-methionine (SAMe) in treating major depression.

Read the detailed description

SAMe is a substance that is naturally produced by the body and is also sold as an over-the-counter drug. Although SAMe has not yet been approved for treating depression, evidence suggests that it has antidepressant properties. This study will determine whether SAMe is safe and effective in treating major depression.

This study will last 24 weeks. Participants will be randomly assigned to receive either the antidepressant escitalopram, SAMe, or placebo for 12 weeks. Participants who respond to treatment at the end of 12 weeks will stay on their regimen for an additional 12 weeks. Participants who do not respond to treatment will enter an open treatment phase where they will receive SAMe and escitalopram for 12 more weeks. Depression scales and self-report questionnaires will be used to assess participants. All participants will receive 3 months of follow-up care, including free medication and clinic visits as necessary.

Conditions: Depression
Being tested: S-adenosyl-l-methionine, Escitalopram, Placebo
Keywords: Depression, Antidepressive Agents, Complementary Therapies
Medical subject headings: Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

S-adenosyl-l-methionineDrug
Also called SAMe
1600 mg per day with possibility of increasing to 3200 mg per day at 6 weeks
EscitalopramDrug
Also called Lexapro
10 mg per day, with possibility of increasing to 20 mg/day at 6 weeks
PlaceboDrug
placebo capsules look like escitalopram capsules and SAMe capsules

Study groups in NCT00101452
Study group	Role	What they receive
S-adenosyl-l-methionine (SAMe)	Experimental	A natural substance Receives: Drug: S-adenosyl-l-methionine
2. Escitalopram	Active comparator	A selective serotonin reuptake inhibitor (SSRI) Receives: Drug: Escitalopram
3. placebo	Placebo comparator	Sugar pill- contains no active ingredients Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Hamilton Rating Scale for Depression (HAM-D)
The change in total HAM-D score between baseline and endpoint was the primary outcomes measure. This measure is a clinician rated inventory of depressive symptoms. All items are scored on a scale of zero to four and the sum of the scores provides the total score for the measure. Scores can range from 0- 68. On this scale, higher scores indicate poorer outcomes.
Measured: baseline and 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2005Jun 2010

First posted11 Jan 2005 (estimated)
Study startApr 2005
Primary completionJun 2010
Study completionJun 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for DepressionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 199 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00101452
Sponsor's protocol ID: R01AT001638-01A1
Other IDs: R01AT001638-01A1
Status last verified: Mar 2017
First submitted: 10 Jan 2005
Last updated: 4 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Undecided

Publications

Mischoulon D, Price LH, Carpenter LL, Tyrka AR, Papakostas GI, Baer L, Dording CM, Clain AJ, Durham K, Walker R, Ludington E, Fava M. A double-blind, randomized, placebo-controlled clinical trial of S-adenosyl-L-methionine (SAMe) versus escitalopram in major depressive disorder. J Clin Psychiatry. 2014 Apr;75(4):370-6. doi: 10.4088/JCP.13m08591.
PubMed 24500245
Sarris J, Price LH, Carpenter LL, Tyrka AR, Ng CH, Papakostas GI, Jaeger A, Fava M, Mischoulon D. Is S-Adenosyl Methionine (SAMe) for Depression Only Effective in Males? A Re-Analysis of Data from a Randomized Clinical Trial. Pharmacopsychiatry. 2015 Jul;48(4-5):141-4. doi: 10.1055/s-0035-1549928. Epub 2015 May 26.
PubMed 26011569
Mischoulon D, Price LH, Carpenter LL, Tyrka AR, Papakostas GI, Fava M. Dr. Mischoulon and colleagues reply. J Clin Psychiatry. 2014 Nov;75(11):e1328-9. doi: 10.4088/JCP.14lr09266a. No abstract available.
PubMed 25470103
Laferton JAC, Vijapura S, Baer L, Clain AJ, Cooper A, Papakostas G, Price LH, Carpenter LL, Tyrka AR, Fava M, Mischoulon D. Mechanisms of Perceived Treatment Assignment and Subsequent Expectancy Effects in a Double Blind Placebo Controlled RCT of Major Depression. Front Psychiatry. 2018 Sep 7;9:424. doi: 10.3389/fpsyt.2018.00424. eCollection 2018.
PubMed 30245644
Admon R, Nickerson LD, Dillon DG, Holmes AJ, Bogdan R, Kumar P, Dougherty DD, Iosifescu DV, Mischoulon D, Fava M, Pizzagalli DA. Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties. Psychol Med. 2015 Jan;45(1):121-31. doi: 10.1017/S0033291714001123. Epub 2014 May 15.
PubMed 25055809

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 4 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-Blind, Placebo-Controlled Study of the Alternative Therapy S-Adenosyl-L-Methionine (SAMe) vs Escitalopram in Major Depressive Disorder (MDD)
ClinicalTrials.gov ID: NCT00101452
Acronym / sponsor ID: R01AT001638-01A1
Conditions: Depression
Keywords: Depression, Antidepressive Agents, Complementary Therapies
Study type: Interventional
Recruitment status: Completed
Enrolment: 199 participants (actual)
Lead sponsor: Maurizio Fava, MDUniversity, hospital or other
Collaborators: National Center for Complementary and Integrative Health (NCCIH)
Study start: Apr 2005
Primary completion: Jun 2010 (actual)
Study completion: Jun 2010 (actual)
First posted: 11 Jan 2005 (estimated)
Results: Posted 31 Dec 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to determine the safety and effectiveness of s-adenosyl-l-methionine (SAMe) in treating major depression.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
S-adenosyl-l-methionine (SAMe)	Experimental	Drug: S-adenosyl-l-methionineA natural substance
2. Escitalopram	Active comparator	Drug: EscitalopramA selective serotonin reuptake inhibitor (SSRI)
3. placebo	Placebo comparator	Drug: PlaceboSugar pill- contains no active ingredients

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Diagnosis of major depression
Score of 25 or higher on the Inventory of Depressive Symptomatology (IDS-C) scale
Score of higher than 2 on the Clinical Global Impression Improvement (CGI) scale
Willing to use acceptable methods of contraception

Key exclusion criteria (16 listed)

Suicidal or homicidal
Unstable illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
Any of the following mental conditions: organic mental disorders; schizophrenia; delusional disorder; psychotic disorders; bipolar disorder; recent bereavement; severe borderline or antisocial personality disorder; panic disorder; or obsessive compulsive disorder
Substance abuse, including alcohol abuse, within 6 months prior to study entry
Uncontrolled seizure disorder, or a seizure disorder controlled with psychotropic anticonvulsants

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
S-adenosyl-l-methionineAlso: SAMe1600 mg per day with possibility of increasing to 3200 mg per day at 6 weeks	Drug	S-adenosyl-l-methionine (SAMe)
EscitalopramAlso: Lexapro10 mg per day, with possibility of increasing to 20 mg/day at 6 weeks	Drug	2. Escitalopram
Placeboplacebo capsules look like escitalopram capsules and SAMe capsules	Drug	3. placebo

Primary outcome

Hamilton Rating Scale for Depression (HAM-D)
Time frame: baseline and 24 weeks
The change in total HAM-D score between baseline and endpoint was the primary outcomes measure. This measure is a clinician rated inventory of depressive symptoms. All items are scored on a scale of zero to four and the sum of the scores provides the total score for the measure. Scores can range from 0- 68. On this scale, higher scores indicate poorer outcomes.

Results and safety

Results posted to the registry on 31 Dec 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
1. SAMe	65	21
2. Escitalopram	69	26
3. Placebo	65	22

Primary outcome: Hamilton Rating Scale for Depression (HAM-D)

Time frame: baseline and 24 weeks. Mean (Standard Deviation). Unit: units on a scale

Measure	1. SAMe n = 59	2. Escitalopram n = 55	3. Placebo n = 52
Value	-6.7 (7.3)	-7.5 (7.4)	-5.7 (7.0)

1. SAMe vs 2. Escitalopram vs 3. Placebo: p <0.05, ANOVA

Population analysed: Based on having at least one post-baseline visit.

Adverse events

Time frame: Adverse events for SAMe, escitalopram, and placebo, were reported during the 12 week double blind course of the study and during the 12-week open cross over phase that followed the acute treatment phase.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
1. SAMe (Weeks 1-12)	0 of 59 (0%)	27 of 59 (45.8%)	0 of 59
2. Escitalopram (Weeks 1-12)	0 of 55 (0%)	32 of 55 (58.2%)	0 of 55
3. Placebo (Weeks 1-12)	0 of 52 (0%)	29 of 52 (55.8%)	0 of 52
4. SAMe (Weeks 12-24, Continuation)	0 of 17 (0%)	14 of 17 (82.4%)	0 of 17
5. Escitalopram (Weeks 12-24, Continuation)	0 of 11 (0%)	12 of 14 (85.7%)	0 of 11
6. Placebo (Weeks 12-24, Continuation)	0 of 15 (0%)	12 of 15 (80%)	0 of 15
7. SAMe Plus Escitalopram (Weeks 12-24, Cross-over)	0 of 43 (0%)	29 of 43 (67.4%)	0 of 43

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 24500245Mischoulon D, Price LH, Carpenter LL, Tyrka AR, Papakostas GI, Baer L, Dording CM, Clain AJ, Durham K, Walker R, Ludington E, Fava M. A double-blind, randomized, placebo-controlled clinical trial of S-adenosyl-L-methionine (SAMe) versus escitalopram in major depressive disorder. J Clin Psychiatry. 2014 Apr;75(4):370-6. doi: 10.4088/JCP.13m08591.
Results publication: PubMed 26011569Sarris J, Price LH, Carpenter LL, Tyrka AR, Ng CH, Papakostas GI, Jaeger A, Fava M, Mischoulon D. Is S-Adenosyl Methionine (SAMe) for Depression Only Effective in Males? A Re-Analysis of Data from a Randomized Clinical Trial. Pharmacopsychiatry. 2015 Jul;48(4-5):141-4. doi: 10.1055/s-0035-1549928. Epub 2015 May 26.
Results publication: PubMed 25470103Mischoulon D, Price LH, Carpenter LL, Tyrka AR, Papakostas GI, Fava M. Dr. Mischoulon and colleagues reply. J Clin Psychiatry. 2014 Nov;75(11):e1328-9. doi: 10.4088/JCP.14lr09266a. No abstract available.
Derived from this study: PubMed 30245644Laferton JAC, Vijapura S, Baer L, Clain AJ, Cooper A, Papakostas G, Price LH, Carpenter LL, Tyrka AR, Fava M, Mischoulon D. Mechanisms of Perceived Treatment Assignment and Subsequent Expectancy Effects in a Double Blind Placebo Controlled RCT of Major Depression. Front Psychiatry. 2018 Sep 7;9:424. doi: 10.3389/fpsyt.2018.00424. eCollection 2018.
Derived from this study: PubMed 25055809Admon R, Nickerson LD, Dillon DG, Holmes AJ, Bogdan R, Kumar P, Dougherty DD, Iosifescu DV, Mischoulon D, Fava M, Pizzagalli DA. Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties. Psychol Med. 2015 Jan;45(1):121-31. doi: 10.1017/S0033291714001123. Epub 2014 May 15.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Maurizio Fava, MD principal investigator

Massachusetts General Hospital

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing S-adenosyl-l-methionine and Escitalopram in people with Depression, run by Maurizio Fava, MD at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hamilton Rating Scale for Depression (HAM-D) (time frame: baseline and 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00101452, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2017.