Clinical trial NCT05724849: Venlafaxine for the Prevention of Depression in Patients With Head and Neck Cancer
Official title: Venlafaxine for the Prevention of Depression in Patients With Head and Neck Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Head and Neck Cancer
Depression
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2023-02-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a pilot double-blinded, randomized, placebo-controlled trial to determine if venlafaxine prevents depression in patients undergoing surgery for Head and Neck Cancer (HNC).

Detailed description: Patients with head and neck cancer (HNC) are disproportionately affected by major depressive disorder (MDD), with up to 50% developing MDD compared to 15-25% of patients with other solid malignancies. The higher rates of depression seen in HNC patients are likely related to treatment-associated disfigurement, voice and swallow dysfunction, and other physical alterations that significantly diminish quality of life. Survivors of HNC have a significantly increased risk of suicide when compared to other cancers. The rate of suicide among HNC survivors is 63.4 suicides per 100,000 person-years, which is three times that of other cancer survivors and second highest only behind pancreatic cancer.

There is evidence to suggest that depression plays a role in HNC prognosis, with studies showing a 25% decrease in overall survival in HNC patients with depression. Despite the prevalence and impact of depression in HNC patients, there has only been one randomized control trial to prevent depression in patients with HNC that showed potential benefit. This study used escitalopram, a selective-serotonin reuptake inhibitor (SSRI). A more appropriate medication would be one that provided mood stabilization as well as pain modulation, since it is known that HNC treatment can lead to long-term opioid use. Serotonin-norepinephrine reuptake inhibitors (SNRIs) provide dual action against serotonergic and noradrenergic receptors and have shown to provide superior pain relief than monoaminergic drugs such as SSRIs.

The investigators hypothesize that venlafaxine will provide mood stabilization and improved pain control in patients undergoing surgical treatment for HNC. The investigators plan to conduct a pilot double-blinded, randomized, placebo-controlled trial using venlafaxine in HNC patients treated with surgery. Patients who screen negative for Bipolar disorder (BPD) based on the screening tool The Mood Disorder Questionnaire (MDQ) as well as for MDD using the Patient Health Questionnaire (PHQ-9) preoperatively (Cohort A) will be randomized to either venlafaxine or placebo and will be assessed throughout the perioperative period with a series of validated self-reported questionnaires regarding depression, anxiety, pain, and other quality of life measures.

Eligibility criteria: Inclusion Criteria:

COHORT A (RCT)

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 18 years or older
4. Have a recently diagnosed cutaneous or mucosal malignancy
5. Scheduled to undergo surgical treatment for their malignancy with curative intent
6. Ability to take medication orally or via gastric tube feeds
7. Willing to adhere to the study drug's dosing protocol
8. Score \<10 on the PHQ-9

COHORT B (Observation cohort)

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 18 years or older
4. Have a recently diagnosed cutaneous or mucosal malignancy
5. Scheduled to undergo surgical treatment for their malignancy with curative intent
6. Ability to take medication orally or via gastric tube feeds
7. Willing to adhere to the study drug's dosing protocol
8. Score \>10 on the PHQ-9

Exclusion Criteria:

COHORT A (RCT)

1. Score \>10 on PHQ-9
2. Score between 5-9 on PHQ-9 and elect for psychotherapy
3. Age less than 18 years
4. Primary malignancy of thyroid or parathyroid origin
5. Currently meet diagnostic criteria for psychosis, schizophrenia, or bipolar disorder
6. Currently receiving medication as treatment for depression or anxiety including: MAO inhibitors, Linezolid, Other SNRIs or SSRIs, Bupropion
7. Known allergic reaction to components of study drug
8. Treatment with another investigational drug or other intervention within 30 days
9. Females of child-bearing age who are pregnant or nursing
10. Inability to speak or understand English

COHORT B (Observation cohort)

1. Score \<10 on PHQ-9
2. Unwillingness or inability to take venlafaxine
3. Age less than 18 years
4. Primary malignancy of thyroid or parathyroid origin
5. Currently receiving medication as treatment for depression or anxiety including: MAO inhibitors, Linezolid, Other SNRIs or SSRIs, Bupropion

7. Known allergic reaction to components of study drug 8. Treatment with another investigational drug or other intervention within 30 days 9. Females of child-bearing age who are pregnant or nursing 10. Inability to speak or understand English

Primary outcomes:
measure: Prevention of Depression
timeFrame: 4 months post-operatively
Secondary outcomes:
measure: Treatment of Depression
timeFrame: 4 months post-operatively
measure: Prevention of Anxiety
timeFrame: 4 months post-operatively
measure: Prevention of Pain
timeFrame: 4 months post-operatively
measure: Prevention of Pain
timeFrame: 4 months post-operatively
measure: Quality of Life Improvement
timeFrame: 4 months post-operatively
Other outcomes:
Locations:
Study officials:
affiliation: Vanderbilt University Medical Center
name: Michael C Topf, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lydiatt WM, Moran J, Burke WJ. A review of depression in the head and neck cancer patient. Clin Adv Hematol Oncol. 2009 Jun;7(6):397-403.
citation: Chhabria KS, Carnaby GD. Psychometric validation of the Center for Epidemiological Studies Depression Scale in Head and Neck Cancer patients. Oral Oncol. 2017 Dec;75:158-162. doi: 10.1016/j.oraloncology.2017.11.010. Epub 2017 Nov 15.
citation: Rieke K, Schmid KK, Lydiatt W, Houfek J, Boilesen E, Watanabe-Galloway S. Depression and survival in head and neck cancer patients. Oral Oncol. 2017 Feb;65:76-82. doi: 10.1016/j.oraloncology.2016.12.014. Epub 2017 Jan 1.
citation: Archer J, Hutchison I, Korszun A. Mood and malignancy: head and neck cancer and depression. J Oral Pathol Med. 2008 May;37(5):255-70. doi: 10.1111/j.1600-0714.2008.00635.x. Epub 2008 Feb 26.
citation: Cramer JD, Johnson JT, Nilsen ML. Pain in Head and Neck Cancer Survivors: Prevalence, Predictors, and Quality-of-Life Impact. Otolaryngol Head Neck Surg. 2018 Nov;159(5):853-858. doi: 10.1177/0194599818783964. Epub 2018 Jun 26.
citation: Friedland CJ. Head and Neck Cancer: Identifying Depression as a Comorbidity Among Patients. Clin J Oncol Nurs. 2019 Feb 1;23(1):99-102. doi: 10.1188/19.CJON.99-102.
citation: Barber B, Dergousoff J, Slater L, Harris J, O'Connell D, El-Hakim H, Biron VL, Mitchell N, Seikaly H. Depression and Survival in Patients With Head and Neck Cancer: A Systematic Review. JAMA Otolaryngol Head Neck Surg. 2016 Mar;142(3):284-8. doi: 10.1001/jamaoto.2015.3171.
citation: Lydiatt WM, Denman D, McNeilly DP, Puumula SE, Burke WJ. A randomized, placebo-controlled trial of citalopram for the prevention of major depression during treatment for head and neck cancer. Arch Otolaryngol Head Neck Surg. 2008 May;134(5):528-35. doi: 10.1001/archotol.134.5.528.
citation: Lydiatt WM, Bessette D, Schmid KK, Sayles H, Burke WJ. Prevention of depression with escitalopram in patients undergoing treatment for head and neck cancer: randomized, double-blind, placebo-controlled clinical trial. JAMA Otolaryngol Head Neck Surg. 2013 Jul;139(7):678-86. doi: 10.1001/jamaoto.2013.3371.
citation: Panwar A, Rieke K, Burke WJ, Sayles H, Lydiatt WM; Prevention of Depression in Patients Being Treated for Head and Neck Cancer Trial (PROTECT) study group. Identification of Baseline Characteristics Associated With Development of Depression Among Patients With Head and Neck Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2018 Nov 1;144(11):1004-1010. doi: 10.1001/jamaoto.2018.2228.
citation: Smith EM, Pang H, Cirrincione C, Fleishman S, Paskett ED, Ahles T, Bressler LR, Fadul CE, Knox C, Le-Lindqwister N, Gilman PB, Shapiro CL; Alliance for Clinical Trials in Oncology. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA. 2013 Apr 3;309(13):1359-67. doi: 10.1001/jama.2013.2813.