SAM-e for the Treatment of Depression in Patients With Parkinson's Disease

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00070941
• Collaborator: National Center for Complementary and Integrative Health (NCCIH) (NIH), Office of Dietary Supplements (ODS) (NIH)
• Enrollment: 29
• Location: 1
• Arms: 3
• Duration (Months): 87
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will test a chemical called s-adenosyl-methionine (SAM-e) for the treatment of depression in patients with Parkinson's disease (PD).

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease; Depression	Drug: SAM-e; Drug: oral escitalopram; Drug: placebo	Phase 2/Phase 3

Detailed Description

PD is commonly associated with depression, but conventional antidepressants have limited efficacy in patients with PD and may exacerbate motor symptoms. SAM-e is available in the United States as a food supplement and is promoted as a mood enhancer. SAM-e improves dopamine transmission, may have a beneficial effect on dopamine receptors, and may be a good alternative to the currently-used antidepressants in patients with PD. This study will investigate whether SAM-e is safe and effective in the treatment of depression associated with PD. The efficacy of SAM-e will be compared to placebo and to escitalopram, a selective serotonin reuptake inhibitor commonly used for the treatment of depression in PD.

Participants in this study will be randomly assigned to receive SAM-e, escitalopram, or placebo for 12 weeks. Some participants may choose to extend treatment for an additional 12 weeks (for a total of 24 weeks on study medication). Participants will have study visits at entry and Weeks 2, 4, 8, and 12. Study visits will include neurological evaluation, psychiatric evaluation, blood tests, and quality of life questionnaires. A telephone interview will be conducted at Week 10.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: SAM-e Treatment of Depression in Parkinson's Disease.
• Study Start Date: Jul 1, 2003
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SAM-e 40 subjects receiving oral SAM-e, 1200mg or 1800mg daily in two divided doses, and placebo escitalopram.	Drug: SAM-e; oral SAM-e in two divided doses, 1200mg or 1800mg daily, with placebo escitalopram.; Other Names: 1 Experimental
Active Comparator: Escitalopram 40 subjects receiving oral escitalopram 20mg or 40 mg daily, in two divided doses, and placebo SAM-e.	Drug: oral escitalopram; 20mg or 30mg daily in two divided doses, along with placebo SAM-e.
Placebo Comparator: Placebo Comparator 20 subjects receiving oral placebo escitalopram and placebo SAM-3 daily in two divided doses.	Drug: placebo; oral placebo escitalopram and oral placebo SAM-e daily in two divided doses.

Outcome Measures

Primary Outcome Measures

1. Change in Hamilton Depression Scale [12 weeks]

   very severe, >23/29; severe, 19-22/29; moderate, 14-18/29; mild, 8-13/29; and no depression, 0-7/29 (Hamilton M., J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62.)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Idiopathic Parkinson's disease as indicated by the presence of at least two of the following signs: resting tremor, rigidity, bradykinesia, or postural reflex impairment

• Stable anti-parkinson medication regimen, with no change in medications in the 4 weeks prior to study entry

• No antidepressant or antipsychotic medications within 30 days prior to study entry

• Agree not to start other pharmacotherapy, psychotherapy, or behavior therapy while participating in the trial

• Acceptable methods of contraception

• Ability to read and/or follow written and oral instructions presented in English

• Sufficient cognitive ability (baseline Mini-Mental Status > 24) to provide informed consent

Exclusion Criteria

• History of cardiac, hepatic, renal, hematologic, respiratory, endocrine, vascular, metabolic, or other systems abnormalities that are clinically relevant in the opinion of study officials

• Certain abnormal laboratory values

• Pregnant or breastfeeding

• Use of an investigational drug within 3 months of study entry

• Use of St. John's Wort or any other "natural" product known to have mood enhancing properties in the 30 days prior to study entry

• Selegiline or other monoamine oxidase inhibitor within the 6 weeks prior to study entry

• Regular usage of anti-anxiety medications or habitual use of sleep medications, although occasional use of certain hypnotics (temazepam, melatonin, or zolpidem) is allowed

• Psychotherapy initiated in the 6 months prior to study entry

• History of bipolar disorder, hypomania, mania, schizophrenia, or other psychotic disorder

• Serious suicidal attempt in the 12 months prior to study entry or serious suicidal tendencies/potential

• Use of dopamine receptor antagonist (metoclopramide, haloperidol)

• Secondary Parkinsonian symptoms due to drugs (including dopamine receptor antagonists), metabolic disorders, cerebrovascular disease, encephalitis, or other degenerative diseases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York University	New York	New York	United States	10003

Sponsors and Collaborators

• NYU Langone Health
• National Center for Complementary and Integrative Health (NCCIH)
• Office of Dietary Supplements (ODS)

Investigators

• Principal Investigator: Alessandro Di Rocco, MD, NYU

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT00070941
• Other Study ID Numbers: R01AT000941-01A1; R01AT000941-01A1; 075255364
• First Posted: Oct 13, 2003
• Last Update Posted: Jul 13, 2016
• Last Verified: Jun 1, 2016

• Keywords provided by NYU Langone Health: Parkinsons Disease; Depression; SAM-e
• Additional relevant MeSH terms: Parkinson Disease; Depression; Depressive Disorder; Citalopram

Study Results

Participant Flow

Recruitment Details	The recruitment dates 01NOV2006-31OCT2008 locations: James Godbold, PH.D. Mount Sinai School of Medicine Steven Ferrando, MD - Weill Medical College of Cornell University Teodoro Bottiglieri, Ph.D. - Baylor College of Medicine Dr. Peter Werner - Albert Einstein College of Medicine

Arm/Group Title	SAM-e	Escitalopram	Placebo Comparator
Arm/Group Description	SAM-e, 1200mg or 2400 mg	oral Escitalopram 10mg or 20m	oral placebo Escitalopram and placebo SAM-e
Period Title: Overall Study
STARTED	12	11	6
COMPLETED	2	3	2
NOT COMPLETED	10	8	4

Baseline Characteristics

Arm/Group Title	SAM-e	Escitalopram	Placebo Comparator	Total
Arm/Group Description	oral SAM-e, 1200mg or 2400 mg	oral Escitalopram 10mg or 20m	oral placebo Escitalopram and placebo SAM-e	Total of all reporting groups
Overall Participants	12	11	6	29
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	6 50%	3 27.3%	0 0%	9 31%
>=65 years	6 50%	8 72.7%	6 100%	20 69%
Sex: Female, Male (Count of Participants)
Female	6 50%	5 45.5%	3 50%	14 48.3%
Male	6 50%	6 54.5%	3 50%	15 51.7%
Region of Enrollment (participants) [Number]
United States	12 100%	11 100%	6 100%	29 100%

Outcome Measures

1. Primary Outcome

Title	Change in Hamilton Depression Scale
Description	very severe, >23/29; severe, 19-22/29; moderate, 14-18/29; mild, 8-13/29; and no depression, 0-7/29 (Hamilton M., J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62.)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SAM-e	Escitalopram	Placebo Comparator
Arm/Group Description	SAM-e, 1200mg or 2400 mg	oral Escitalopram 10mg or 20m	oral placebo Escitalopram and placebo SAM-e
Measure Participants	12	8	4
Baseline Visit Measurement	17 (4.8)	17.5 (5.4)	20.7 (3.2)
Week 12 Measurement	11.4 (7.3)	5.3 (3.3)	16.2 (3.6)

Adverse Events

Arm/Group Title	SAM-e		Oral Escitalopram		Placebo
Arm/Group Description	Group A/Forty patients receiving oral SAM-e, 1200mg or 2400 mg		Group B/Forty patients receiving oral Escitalopram 10mg or 20m		Group C/Twenty patients receiving oral placebo Escitalopram an
All Cause Mortality
	SAM-e		Oral Escitalopram		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	SAM-e		Oral Escitalopram		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		0/11 (0%)		3/6 (50%)
General disorders
Death	0/12 (0%)		0/11 (0%)		1/6 (16.7%)
Infections and infestations
Abscess	0/12 (0%)		0/11 (0%)		1/6 (16.7%)
Injury, poisoning and procedural complications
Fall	0/12 (0%)		0/11 (0%)		1/6 (16.7%)
Vascular disorders
Hypotension Orthostatic	1/12 (8.3%)		0/11 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	SAM-e		Oral Escitalopram		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/12 (100%)		8/11 (72.7%)		6/6 (100%)
Blood and lymphatic system disorders
POLYCYTHAEMIA	0/12 (0%)		0/11 (0%)		1/6 (16.7%)
Cardiac disorders
CHEST PAIN	1/12 (8.3%)		0/11 (0%)		0/6 (0%)
TACHYCARDIA	0/12 (0%)		2/11 (18.2%)		1/6 (16.7%)
Ear and labyrinth disorders
BALANCE DIFFICULTY	0/12 (0%)		2/11 (18.2%)		0/6 (0%)
Eye disorders
INDIGESTION	0/12 (0%)		1/11 (9.1%)		0/6 (0%)
VISION BLURRED	2/12 (16.7%)		5/11 (45.5%)		2/6 (33.3%)
Gastrointestinal disorders
ABDOMINAL PAIN	2/12 (16.7%)		0/11 (0%)		0/6 (0%)
BLOATING	0/12 (0%)		1/11 (9.1%)		0/6 (0%)
CONSTIPATION	6/12 (50%)		2/11 (18.2%)		3/6 (50%)
DIARRHOEA	1/12 (8.3%)		0/11 (0%)		1/6 (16.7%)
MOUTH DRY	3/12 (25%)		4/11 (36.4%)		3/6 (50%)
NAUSEA	4/12 (33.3%)		3/11 (27.3%)		5/6 (83.3%)
STOMACH UPSET	1/12 (8.3%)		0/11 (0%)		0/6 (0%)
VOMITING	1/12 (8.3%)		0/11 (0%)		1/6 (16.7%)
General disorders
PAIN	0/12 (0%)		1/11 (9.1%)		0/6 (0%)
WEAKNESS GENERALIZED	2/12 (16.7%)		3/11 (27.3%)		3/6 (50%)
Injury, poisoning and procedural complications
FALL	2/12 (16.7%)		1/11 (9.1%)		2/6 (33.3%)
LEG PAIN	0/12 (0%)		1/11 (9.1%)		0/6 (0%)
Metabolism and nutrition disorders
ANOREXIA	5/12 (41.7%)		2/11 (18.2%)		2/6 (33.3%)
APPETITE DECREASED	0/12 (0%)		1/11 (9.1%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
MUSCLE RIGIDITY	0/12 (0%)		1/11 (9.1%)		0/6 (0%)
MUSCLE WEAKNESS	0/12 (0%)		1/11 (9.1%)		0/6 (0%)
Nervous system disorders
DIZZINESS	2/12 (16.7%)		4/11 (36.4%)		3/6 (50%)
DROWSINESS	4/12 (33.3%)		2/11 (18.2%)		2/6 (33.3%)
DYSKINESIA	0/12 (0%)		0/11 (0%)		1/6 (16.7%)
FAINTNESS	1/12 (8.3%)		3/11 (27.3%)		3/6 (50%)
HEADACHE	3/12 (25%)		4/11 (36.4%)		1/6 (16.7%)
LETHARGY	1/12 (8.3%)		0/11 (0%)		0/6 (0%)
SYNCOPE	1/12 (8.3%)		0/11 (0%)		0/6 (0%)
TREMOR	4/12 (33.3%)		3/11 (27.3%)		2/6 (33.3%)
TREMOR COARSE	0/12 (0%)		0/11 (0%)		1/6 (16.7%)
Psychiatric disorders
AGITATION	3/12 (25%)		1/11 (9.1%)		1/6 (16.7%)
ANXIETY	1/12 (8.3%)		0/11 (0%)		0/6 (0%)
CONFUSION	2/12 (16.7%)		0/11 (0%)		0/6 (0%)
EXCITABILITY	1/12 (8.3%)		0/11 (0%)		1/6 (16.7%)
HALLUCINATION AUDITORY	0/12 (0%)		0/11 (0%)		1/6 (16.7%)
HALLUCINATION VISUAL	0/12 (0%)		0/11 (0%)		2/6 (33.3%)
INSOMNIA	4/12 (33.3%)		3/11 (27.3%)		5/6 (83.3%)
LIBIDO DECREASED	1/12 (8.3%)		0/11 (0%)		0/6 (0%)
VIVID DREAMING	1/12 (8.3%)		0/11 (0%)		0/6 (0%)
Renal and urinary disorders
URINARY FREQUENCY	1/12 (8.3%)		0/11 (0%)		0/6 (0%)
URINARY RETENTION	0/12 (0%)		0/11 (0%)		1/6 (16.7%)
Skin and subcutaneous tissue disorders
DERMATITIS	1/12 (8.3%)		1/11 (9.1%)		0/6 (0%)
Vascular disorders
BLOOD PRESSURE INCREASED	0/12 (0%)		0/11 (0%)		1/6 (16.7%)
HYPOTENSION ORTHOSTATIC	1/12 (8.3%)		0/11 (0%)		1/6 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

According to the NIH -grant that supported this clinical trial all publications must be reported to the grant office prior to the release of publications. Statement from NIH award letter: This includes manuscripts submitted or accepted for publication to the awarding component. Report only those publications resulting directly from this grant and those publications. If there have been no publications, so state.