Breast CancerPhase 2NCT03847311
Sulfasalazine in Decreasing Opioids Requirements in Breast Cancer Patients
A Phase 2 study testing Sulfasalazine in people with Breast Cancer and Chronic Pain Due to Malignancy (Finding), run by University of Arizona at 2 sites in United States.
Trial summary
Cancer in general, and breast cancer in specific, is a significant health problem in the USA and the rest of the world. With the improvement of new surgical approaches and chemotherapies to manage breast cancer, the number of patients with breast cancer are now living longer. Read more about this study
- Who is it for?
- Ages 18 to 94 years, women only
- Conditions the study is for
- Breast Cancer, Chronic Pain Due to Malignancy (Finding)
- What is being tested?
- Sulfasalazine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 May 2021to 9 Oct 2023
- Phase
- Phase 2
- 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 94 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patient age 18 - <95 years old capable of understanding and providing consent in English and capable of complying with the outcome used.
- Diagnosis of cancer with pain moderate to severe pain on stable doses of opioids
- 3-day average numeric pain rating score (NPRS) for pain of at least 5/10 at baseline evaluation.
- Patient consents to double blind design of the experiment in a shared decision- making process with the treating physician.
- Pain duration of at least 6 weeks or more.
- Prognosis greater than 6 months.
- Able to take oral medication
Who cannot join
- Those receiving remuneration for their pain treatment (e.g., disability, worker's compensation).
- Those involved in active litigation relevant to their pain.
- Subjects with intestinal or urinary obstruction or at risk of such disorders.
- Porphyria
- Blood dyscrasias, hepatic or renal disease.
- Taking medications that may interact with sulfasalazine.
Show all 13Show fewer
- Taking Lapatinib or Digoxin.
- No sustained hypercalcemia.
- Hypersensitivity to sulfasalazine, its metabolites, sulfonamides, or salicylates.
- The Subject is incarcerated.
- Those unable to read English and complete the assignment in English.
- Addictive behavior, severe clinical depression, or psychotic features.
- Possible pregnancy or lactation.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Banner University Medical Center South
Tucson, Arizona, 85713
Banner University Medical Center North Campus
Tucson, Arizona, 85719
About this study
Official title: Double Blind Trial Investigating the Role of Sulfasalazine in Decreasing Opioids Requirements in Breast Cancer Patients
Cancer in general, and breast cancer in specific, is a significant health problem in the USA and the rest of the world. With the improvement of new surgical approaches and chemotherapies to manage breast cancer, the number of patients with breast cancer are now living longer. This great achievement created an unexpected problem. For some breast cancer patients, with bone metastases, the pain is worse than the cancer. The golden standard to manage pain is opioids. Patients with cancer-induced bone pain are now taking increasing doses of opioids to control their pain. Sadly, opioids come with significant side effects that limit the amount of opioids that can be safely given. Many attempts have been tried to create better regiments for pain control to lower the need for opioids. There has not been significant success in that area. A better approach would be to add a non-opioid agent that has dual mechanisms of action. This may create synergism to better control pain while lowering the doses of opioids needed and lowering side effects. Sulfasalazine poses such quality it is a safe anti-inflammatory drug with established safety profile. It has been in use for over 50 years for the treatment of inflammatory conditions such as arthritis. In addition to its anti-inflammatory characteristics, sulfasalazine has the capacity to decrease the survival of cancer cells, also to lower the number of inflammatory mediators released by cancer cells. In short, sulfasalazine inhibit the influx of cysteine into cancer cells and the efflux of glutamate. Cysteine is needed for cell survival against oxidative stress, while glutamate activate pain receptors. Therefore, sulfasalazine will act as anti-inflammatory, an agent to accelerate cancer cells death and decreasing the released glutamate which activate pain receptors. This one agent with 3 mechanisms of actions may lower the amount of opioid needed for these patients while maintaining or improving their pain. Lowering of opioid dosing may also improve the side effects associated with opioid use. The purpose of this trial is to co-administer sulfasalazine with opioids to cancer patients and characterize their pain and the opioid use. Our hypothesis is that adding sulfasalazine to the pain medication, will lower the amount of opioids used and lower the side effects. This may improve the quality of life for patients and decrease the risks of using high amount of opioids for the patients, their families, and society in general.
Read the detailed description
In the United States, approximately one in two men and one in three women will develop cancer. Today, more than 15 million people live with cancer in the United States alone. The direct annual medical cost of cancer is over 86 billion US dollars. The indirect cost, representing loss of wages and productivity, exceeds 130 billion US dollars annually. It is estimated that 90% of all cancer patients report pain. About 63% of patients with advanced stage cancer or with metastasis suffer from pain that is classified as "moderate to severe". The majority of cancer patients suffer from excruciating pain. Even those who survive cancer may still experience pain. Of all cancer survivors, 59% report pain secondary to chemotherapy. Even after patients are cured from their cancer, 33% of these patients will still suffer from severe pain due to their chemotherapy. Inadequate pain management results in 67% of patients with severe pain. Notably, 32% of cancer patients reported a desire for suicide secondary to their pain.
Opioids have been the gold standard to treat cancer pain. Sadly, there are many side effects associated with chronic opioid use. It has been shown in animal models that chronic use of opioids has been associated with paradoxical effects. Rats that have been exposed to chronic opioids developed hyperalgesia, which is an exaggerated response to a painful stimulus and allodynia, which is a painful response to a non-painful stimulus. There have been several mechanisms proposed to explain the paradoxical hyperalgesia phenomena observed. This phenomenon has been recognized in patients inflected with chronic pain and managed with chronic opioid. It has been long observed that patients with chronic pain require gradually increasing doses of opioids. The reasons for this increase in opioid requirement may be complicated. While the progression of the disease may play a significant part in increasing doses of opioid, other factors such as tolerance and opioid induced hyperalgesia cannot be ignored. Tolerance is a characteristic of opioids that is well investigated and results in increasing the doses of opioids to maintain the original analgesic effects. Changing of brain circuitry enables opioids to play a sinister role allowing it to produce pain. Additionally, patients develop physical dependence with their use of opioids. A more significant aspect of chronic use of opioid is the psychological dependence on opioids. While its understandable and necessary for cancer patients to have opioids to control their pain, finding adjuvant pain control therapy may lessen the amount of opioids needed. Using neuropathic pain medications as adjuvants to supplement opioids had mixed results. Therefore, a different agent with different mechanism is action may be needed for better pain control with less opioids.
Cancer cells have high metabolic rate that generate high oxidative stress burden. Cancer cells require glutathione to combat oxidative stress for survival. Cysteine is required for the synthesis of glutathione. Cells acquire cysteine be exchanging intracellular glutamate for the extra cellular cysteine through the Cysteine/Glutamate antiporter. Excreting glutamate results in increased pain through the activation of N-methyl-D-aspartate receptor (NMDA). If an agent can be identified that inhibits the Cysteine/Glutamate antiporter, the cancer cells will have less chances of survival secondary to decreased glutathione that's is needed for protection from oxidative stress. Additionally, decreased amount of the glutamate secreted from the cells may lower the amount of pain produced.
Sulfasalazine is a safe and well-established anti-inflammatory drug with potent inhibitory properties of the cysteine/glutamate antiporter. Utilizing sulfasalazine for cancer patients, in conjunction with opioids, may reduce the amount of opioids needed in two different methods. First, sulfasalazine may decrease the survival rate of cancer cells, thus lowering the mechanical burden of the cancer. Second, sulfasalazine may decrease the amount of glutamate released by cancer cell resulting in less activation of the NMDA receptor.
The investigator proposes a clinical trial to administer sulfasalazine to initially focus on breast cancer patients with pain. The pain may be from the primary tumor or from metastasis. The investigator hypothesis that sulfasalazine will reduce cancer pain, the amount of the opioids needed, and the undesirable side effects associated with high doses of opioid.
- Being tested
- Sulfasalazine, Placebos
- Medical subject headings
- Breast Neoplasms, Signs and Symptoms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SulfasalazineDrug
Also called Active treatment
This group will receive supplies for 3 months of sulfasalazine at an initial dose of 0.5 gram three times a day for a week then at a dose of 1 gram three times a day for the remainder of the 3 months. Subjects will be asked to take their medications with every meal in addition to their regular pain medications.
PlacebosDrug
Also called Non-active
This group will receive supplies for 3 months of sugar pills three times a day for 3 months. Subjects will be asked to take their medications with every meal in addition to their regular pain medications.
| Study group | Role | What they receive |
|---|---|---|
| Placebos | Placebo comparator | Subjects will receive sugar pill. Receives: Drug: Placebos |
| Sulfasalazine | Active comparator | Subjects will receive the active drug. Receives: Drug: Sulfasalazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Pain Relief.
Brief Pain Inventory (BPI) pain severity score. Scale range: 0 (no pain) to 10 (worst pain imaginable) Higher values represent a worse outcome.
Measured: Twelve weeks
Secondary outcomes (1)
Decrease Opiate Dose.
Morphine Milligram Equivalents (MME) per day at 12 weeks.
Measured: Twelve weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2019
- Study start3 May 2021
- Primary completion9 Oct 2023
- Study completion9 Oct 2023
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 (19)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double blind study
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Mohab Ibrahim, PhD MD, University of Arizona
- Investigators
- Mohab M Ibrahim, PhD., MD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03847311
- Sponsor's protocol ID
- 1605576856
- Other IDs
- 5R21CA245411-02
- Status last verified
- Dec 2024
- First submitted
- 18 Feb 2019
- Last updated
- 9 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lifetime Probability of Developing and Dying From Cancer for 23 sites, 2009-2011. 2014.
Manchikanti L, Helm S 2nd, Fellows B, Janata JW, Pampati V, Grider JS, Boswell MV. Opioid epidemic in the United States. Pain Physician. 2012 Jul;15(3 Suppl):ES9-38.
PubMed 22786464Carinci AJ, Mao J. Pain and opioid addiction: what is the connection? Curr Pain Headache Rep. 2010 Feb;14(1):17-21. doi: 10.1007/s11916-009-0086-x.
PubMed 20425210Starrels JL, Becker WC, Alford DP, Kapoor A, Williams AR, Turner BJ. Systematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain. Ann Intern Med. 2010 Jun 1;152(11):712-20. doi: 10.7326/0003-4819-152-11-201006010-00004.
PubMed 20513829Bekhit MH. Opioid-induced hyperalgesia and tolerance. Am J Ther. 2010 Sep-Oct;17(5):498-510. doi: 10.1097/MJT.0b013e3181ed83a0.
PubMed 20844348Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011 Mar-Apr;14(2):145-61.
PubMed 21412369Mao J, Sung B, Ji RR, Lim G. Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity. J Neurosci. 2002 Sep 15;22(18):8312-23. doi: 10.1523/JNEUROSCI.22-18-08312.2002.
PubMed 12223586Vanderah TW, Suenaga NM, Ossipov MH, Malan TP Jr, Lai J, Porreca F. Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance. J Neurosci. 2001 Jan 1;21(1):279-86. doi: 10.1523/JNEUROSCI.21-01-00279.2001.
PubMed 11150345Arner S, Rawal N, Gustafsson LL. Clinical experience of long-term treatment with epidural and intrathecal opioids--a nationwide survey. Acta Anaesthesiol Scand. 1988 Apr;32(3):253-9. doi: 10.1111/j.1399-6576.1988.tb02725.x.
PubMed 3364150Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S, Koch T, Evans CJ, Christie MJ. Regulation of mu-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Pharmacol Rev. 2013 Jan 15;65(1):223-54. doi: 10.1124/pr.112.005942. Print 2013 Jan.
PubMed 23321159Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med. 2003 Nov 13;349(20):1943-53. doi: 10.1056/NEJMra025411. No abstract available.
PubMed 14614170Bar Ad V. Gabapentin for the treatment of cancer-related pain syndromes. Rev Recent Clin Trials. 2010 Sep;5(3):174-8. doi: 10.2174/157488710792007310.
PubMed 20482492Takahashi H, Shimoyama N. A prospective open-label trial of gabapentin as an adjuvant analgesic with opioids for Japanese patients with neuropathic cancer pain. Int J Clin Oncol. 2010 Feb;15(1):46-51. doi: 10.1007/s10147-009-0009-1.
PubMed 20072794Estrela JM, Ortega A, Obrador E. Glutathione in cancer biology and therapy. Crit Rev Clin Lab Sci. 2006;43(2):143-81. doi: 10.1080/10408360500523878.
PubMed 16517421Griffith OW. Biologic and pharmacologic regulation of mammalian glutathione synthesis. Free Radic Biol Med. 1999 Nov;27(9-10):922-35. doi: 10.1016/s0891-5849(99)00176-8.
PubMed 10569625
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind Trial Investigating the Role of Sulfasalazine in Decreasing Opioids Requirements in Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT03847311
- Acronym / sponsor ID
- 1605576856
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 3 May 2021 (actual)
- Primary completion
- 9 Oct 2023 (actual)
- Study completion
- 9 Oct 2023 (actual)
- First posted
- 20 Feb 2019 (actual)
- Results
- Posted 9 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cancer in general, and breast cancer in specific, is a significant health problem in the USA and the rest of the world. With the improvement of new surgical approaches and chemotherapies to manage breast cancer, the number of patients with breast cancer are now living longer. This great achievement created an unexpected problem. For some breast cancer patients, with bone metastases, the pain is worse than the cancer. The golden standard to manage pain is opioids. Patients with cancer-induced bone pain are now taking increasing doses of opioids to control their pain. Sadly, opioids come with significant side effects that limit the amount of opioids that can be safely given. Many attempts have been tried to create better regiments for pain control to lower the need for opioids. There has not been significant success in that area. A better approach would be to add a non-opioid agent that has dual mechanisms of action. This may create synergism to better control pain while lowering the doses of opioids needed and lowering side effects. Sulfasalazine poses such quality it is a safe anti-inflammatory drug with established safety profile. It has been in use for over 50 years for the treatment of inflammatory conditions such as arthritis. In addition to its anti-inflammatory characteristics, sulfasalazine has the capacity to decrease the survival of cancer cells, also to lower the number of inflammatory mediators released by cancer cells. In short, sulfasalazine inhibit the influx of cysteine into cancer cells and the efflux of glutamate. Cysteine is needed for cell survival against oxidative stress, while glutamate activate pain receptors. Therefore, sulfasalazine will act as anti-inflammatory, an agent to accelerate cancer cells death and decreasing the released glutamate which activate pain receptors. This one agent with 3 mechanisms of actions may lower the amount of opioid needed for these patients while maintaining or improving their pain. Lowering of opioid dosing may also improve the side effects associated with opioid use. The purpose of this trial is to co-administer sulfasalazine with opioids to cancer patients and characterize their pain and the opioid use. Our hypothesis is that adding sulfasalazine to the pain medication, will lower the amount of opioids used and lower the side effects. This may improve the quality of life for patients and decrease the risks of using high amount of opioids for the patients, their families, and society in general.
Detailed description
In the United States, approximately one in two men and one in three women will develop cancer. Today, more than 15 million people live with cancer in the United States alone. The direct annual medical cost of cancer is over 86 billion US dollars. The indirect cost, representing loss of wages and productivity, exceeds 130 billion US dollars annually. It is estimated that 90% of all cancer patients report pain. About 63% of patients with advanced stage cancer or with metastasis suffer from pain that is classified as "moderate to severe". The majority of cancer patients suffer from excruciating pain. Even those who survive cancer may still experience pain. Of all cancer survivors, 59% report pain secondary to chemotherapy. Even after patients are cured from their cancer, 33% of these patients will still suffer from severe pain due to their chemotherapy. Inadequate pain management results in 67% of patients with severe pain. Notably, 32% of cancer patients reported a desire for suicide secondary to their pain.
Opioids have been the gold standard to treat cancer pain. Sadly, there are many side effects associated with chronic opioid use. It has been shown in animal models that chronic use of opioids has been associated with paradoxical effects. Rats that have been exposed to chronic opioids developed hyperalgesia, which is an exaggerated response to a painful stimulus and allodynia, which is a painful response to a non-painful stimulus. There have been several mechanisms proposed to explain the paradoxical hyperalgesia phenomena observed. This phenomenon has been recognized in patients inflected with chronic pain and managed with chronic opioid. It has been long observed that patients with chronic pain require gradually increasing doses of opioids. The reasons for this increase in opioid requirement may be complicated. While the progression of the disease may play a significant part in increasing doses of opioid, other factors such as tolerance and opioid induced hyperalgesia cannot be ignored. Tolerance is a characteristic of opioids that is well investigated and results in increasing the doses of opioids to maintain the original analgesic effects. Changing of brain circuitry enables opioids to play a sinister role allowing it to produce pain. Additionally, patients develop physical dependence with their use of opioids. A more significant aspect of chronic use of opioid is the psychological dependence on opioids. While its understandable and necessary for cancer patients to have opioids to control their pain, finding adjuvant pain control therapy may lessen the amount of opioids needed. Using neuropathic pain medications as adjuvants to supplement opioids had mixed results. Therefore, a different agent with different mechanism is action may be needed for better pain control with less opioids.
Cancer cells have high metabolic rate that generate high oxidative stress burden. Cancer cells require glutathione to combat oxidative stress for survival. Cysteine is required for the synthesis of glutathione. Cells acquire cysteine be exchanging intracellular glutamate for the extra cellular cysteine through the Cysteine/Glutamate antiporter. Excreting glutamate results in increased pain through the activation of N-methyl-D-aspartate receptor (NMDA). If an agent can be identified that inhibits the Cysteine/Glutamate antiporter, the cancer cells will have less chances of survival secondary to decreased glutathione that's is needed for protection from oxidative stress. Additionally, decreased amount of the glutamate secreted from the cells may lower the amount of pain produced.
Sulfasalazine is a safe and well-established anti-inflammatory drug with potent inhibitory properties of the cysteine/glutamate antiporter. Utilizing sulfasalazine for cancer patients, in conjunction with opioids, may reduce the amount of opioids needed in two different methods. First, sulfasalazine may decrease the survival rate of cancer cells, thus lowering the mechanical burden of the cancer. Second, sulfasalazine may decrease the amount of glutamate released by cancer cell resulting in less activation of the NMDA receptor.
The investigator proposes a clinical trial to administer sulfasalazine to initially focus on breast cancer patients with pain. The pain may be from the primary tumor or from metastasis. The investigator hypothesis that sulfasalazine will reduce cancer pain, the amount of the opioids needed, and the undesirable side effects associated with high doses of opioid.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double blind study
| Arm | Type | Receives |
|---|---|---|
| Placebos | Placebo comparator | Drug: PlacebosSubjects will receive sugar pill. |
| Sulfasalazine | Active comparator | Drug: SulfasalazineSubjects will receive the active drug. |
Who may qualify
- Ages
- 18 to 94 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult patient age 18 - <95 years old capable of understanding and providing consent in English and capable of complying with the outcome used.
- Diagnosis of cancer with pain moderate to severe pain on stable doses of opioids
- 3-day average numeric pain rating score (NPRS) for pain of at least 5/10 at baseline evaluation.
- Patient consents to double blind design of the experiment in a shared decision- making process with the treating physician.
- Pain duration of at least 6 weeks or more.
Key exclusion criteria (13 listed)
- Those receiving remuneration for their pain treatment (e.g., disability, worker's compensation).
- Those involved in active litigation relevant to their pain.
- Subjects with intestinal or urinary obstruction or at risk of such disorders.
- Porphyria
- Blood dyscrasias, hepatic or renal disease.
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 |
|---|---|---|
| SulfasalazineAlso: Active treatmentThis group will receive supplies for 3 months of sulfasalazine at an initial dose of 0.5 gram three times a day for a week then at a dose of 1 gram three times a day for the remainder of the 3 months. Subjects will be asked to take their medications with every meal in addition to their regular pain medications. | Drug | Sulfasalazine |
| PlacebosAlso: Non-activeThis group will receive supplies for 3 months of sugar pills three times a day for 3 months. Subjects will be asked to take their medications with every meal in addition to their regular pain medications. | Drug | Placebos |
Primary outcome
Overall Pain Relief.
Time frame: Twelve weeks
Brief Pain Inventory (BPI) pain severity score. Scale range: 0 (no pain) to 10 (worst pain imaginable) Higher values represent a worse outcome.
1 secondary outcome
Decrease Opiate Dose.
Time frame: Twelve weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundLifetime Probability of Developing and Dying From Cancer for 23 sites, 2009-2011. 2014.
- Background: PubMed 22786464Manchikanti L, Helm S 2nd, Fellows B, Janata JW, Pampati V, Grider JS, Boswell MV. Opioid epidemic in the United States. Pain Physician. 2012 Jul;15(3 Suppl):ES9-38.
- Background: PubMed 20425210Carinci AJ, Mao J. Pain and opioid addiction: what is the connection? Curr Pain Headache Rep. 2010 Feb;14(1):17-21. doi: 10.1007/s11916-009-0086-x.
- Background: PubMed 20513829Starrels JL, Becker WC, Alford DP, Kapoor A, Williams AR, Turner BJ. Systematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain. Ann Intern Med. 2010 Jun 1;152(11):712-20. doi: 10.7326/0003-4819-152-11-201006010-00004.
- Background: PubMed 20844348Bekhit MH. Opioid-induced hyperalgesia and tolerance. Am J Ther. 2010 Sep-Oct;17(5):498-510. doi: 10.1097/MJT.0b013e3181ed83a0.
- Background: PubMed 21412369Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011 Mar-Apr;14(2):145-61.
- Background: PubMed 12223586Mao J, Sung B, Ji RR, Lim G. Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity. J Neurosci. 2002 Sep 15;22(18):8312-23. doi: 10.1523/JNEUROSCI.22-18-08312.2002.
- Background: PubMed 11150345Vanderah TW, Suenaga NM, Ossipov MH, Malan TP Jr, Lai J, Porreca F. Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance. J Neurosci. 2001 Jan 1;21(1):279-86. doi: 10.1523/JNEUROSCI.21-01-00279.2001.
- Background: PubMed 3364150Arner S, Rawal N, Gustafsson LL. Clinical experience of long-term treatment with epidural and intrathecal opioids--a nationwide survey. Acta Anaesthesiol Scand. 1988 Apr;32(3):253-9. doi: 10.1111/j.1399-6576.1988.tb02725.x.
- Background: PubMed 23321159Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S, Koch T, Evans CJ, Christie MJ. Regulation of mu-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Pharmacol Rev. 2013 Jan 15;65(1):223-54. doi: 10.1124/pr.112.005942. Print 2013 Jan.
- Background: PubMed 14614170Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med. 2003 Nov 13;349(20):1943-53. doi: 10.1056/NEJMra025411. No abstract available.
- Background: PubMed 20482492Bar Ad V. Gabapentin for the treatment of cancer-related pain syndromes. Rev Recent Clin Trials. 2010 Sep;5(3):174-8. doi: 10.2174/157488710792007310.
- Individual participant dataSharing planned: No
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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.
Mohab M Ibrahim, PhD., MD principal investigator
University of Arizona
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sulfasalazine in people with Breast Cancer and Chronic Pain Due to Malignancy (Finding), run by University of Arizona 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 7 inclusion and 13 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 9 Jan 2025. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2025). 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?
Overall Pain Relief. (time frame: Twelve 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 NCT03847311, which also lists 19 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 9 Jan 2025.