Paricalcitol for Chronic Pancreatitis

(ALLIANCE Trial)

Recruiting at 2 trial locations

Overseen By Arax Shanlian

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Cedars-Sinai Medical Center

Disqualifiers: Pregnancy, Pancreatic tumors, Transplant, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called paricalcitol for individuals with chronic pancreatitis, a condition where the pancreas remains inflamed over a long period, causing pain and digestive issues. Researchers aim to determine if this treatment is feasible and acceptable for patients. Participants will take either paricalcitol or a placebo (a pill with no active ingredient) once a day for 12 months. Suitable candidates include those with chronic pancreatitis without gallstone issues, who haven't undergone pancreatic surgery, and can regularly take oral medication. As an Early Phase 1 trial, this study seeks to gather initial insights into how paricalcitol works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

Is there any evidence suggesting that paricalcitol is likely to be safe for humans?

Research has shown that paricalcitol is generally safe for people. It has been used successfully for many years to treat secondary hyperparathyroidism, a condition common in those with kidney issues, indicating it is well-tolerated in these treatments. Studies have found that doses up to 7 mcg/kg per week can be administered safely without causing serious side effects, such as excessive calcium in the blood. Overall, paricalcitol has a good safety record based on its use in other conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for chronic pancreatitis, which typically include enzyme supplements and pain management strategies, Paricalcitol offers a unique approach by targeting the inflammation associated with this condition. Paricalcitol is a form of vitamin D that not only helps regulate calcium levels but also has potential anti-inflammatory effects, which could address one of the root issues in chronic pancreatitis. Researchers are excited about Paricalcitol because it represents a shift towards treating inflammation directly, potentially providing an alternative for patients who do not respond well to existing therapies.

What evidence suggests that paricalcitol might be an effective treatment for chronic pancreatitis?

Research has shown that paricalcitol, a type of vitamin D, may slow the growth of pancreatic cancer cells. Lab and animal studies have observed this effect. Paricalcitol reduces the activity of cells that support tumors and shrinks the tumors themselves, potentially improving survival rates in these studies. It is already safely used for other health issues, such as certain kidney-related conditions. In this trial, participants will receive either paricalcitol or a placebo to study its effects on chronic pancreatitis. Researchers hope that paricalcitol's ability to control cell growth and reduce inflammation might benefit people with chronic pancreatitis. More research is needed to confirm its effectiveness for this condition. ^{2 5 6 7 8}

Who Is on the Research Team?

Stephen Pandol, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

Adults aged 18-75 with Chronic Pancreatitis not caused by gallstones, medications, trauma or autoimmune issues can join. They must be able to take oral meds, have normal calcium/phosphate/parathyroid levels, and use effective contraception if of reproductive potential. Exclusions include organ transplant history, HIV/AIDS, MRI intolerance, certain pancreas-related conditions or surgeries.

Inclusion Criteria

My chronic pancreatitis is not caused by gallstones, medications, trauma, or an autoimmune condition.

I am willing and able to follow all study requirements.

No involvement in any interventional trials currently or within 6 months of enrollment

Exclusion Criteria

I have had pancreatitis due to an autoimmune disease, injury, or a severe attack causing duct issues.

My pancreatic tumor is one of several types, including adenocarcinoma or a suspected large cyst.

Currently incarcerated

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Paricalcitol or placebo once daily for 12 months

12 months

3 visits (in-person) at Screening/Randomization, Month 6, Month 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Paricalcitol
• Placebo

Trial Overview The trial is testing the safety and acceptability of paricalcitol for treating Chronic Pancreatitis compared to a placebo. Participants will receive either the actual drug or a dummy pill without any therapeutic effect to see if there's an improvement in their condition.

How Is the Trial Designed?

Group I: Paricalcitol Experimental Treatment 1 Intervention

Participants receive Paricalcitol 2mcg capsule once daily for 12 months.

Group II: Placebo Placebo Group 1 Intervention

Participants receive Paricalcitol Placebo capsule matching Paricalcitol once daily for 12 months.

Paricalcitol is already approved in United States, European Union for the following indications:

Approved in United States as Zemplar for:

• Secondary hyperparathyroidism associated with chronic kidney disease

Approved in European Union as Paricalcitol for:

• Secondary hyperparathyroidism associated with chronic kidney disease

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Paricalcitol is an effective treatment for secondary hyperparathyroidism in patients with chronic renal failure, as it significantly reduces elevated parathyroid hormone (PTH) levels and is well tolerated in both adults and children.

In clinical trials, paricalcitol demonstrated similar efficacy and safety profiles compared to calcitriol, with no significant increase in the risk of prolonged hypercalcemia or elevated calcium-phosphorus product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paricalcitol: a review of its use in the management of secondary hyperparathyroidism. Robinson, DM., Scott, LJ.[2018]

Paricalcitol is a synthetic vitamin D2 analog that effectively reduces elevated parathyroid hormone (PTH) levels in patients with secondary hyperparathyroidism due to chronic renal failure, and it is well tolerated in both adults and children.

In clinical trials, paricalcitol demonstrated similar efficacy to calcitriol while having a comparable safety profile, particularly regarding the risk of prolonged hypercalcemia, making it a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on paricalcitol in secondary hyperparathyroidism. Robinson, DM., Scott, LJ.[2019]

Vitamin D deficiency is linked to both acute and chronic pancreatitis, suggesting that vitamin D plays a significant role in the inflammation and fibrosis associated with these conditions.

Current evidence indicates that assessing and managing vitamin D levels could be crucial in treating pancreatitis, although more research is needed to fully understand its protective effects and optimal supplementation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D and Pancreatitis: A Narrative Review of Current Evidence. Cai, F., Hu, C., Chen, CJ., et al.[2022]

The new vitamin D3 analogue, 22-oxa-calcitriol, showed significantly greater anti-proliferative effects on pancreatic cancer cell lines compared to calcitriol, particularly in inhibiting the growth of BxPC-3 xenografts in mice without causing hypercalcemia.

Both 22-oxa-calcitriol and calcitriol caused cell cycle arrest in some pancreatic cancer cell lines, but the effectiveness of these treatments was not solely determined by the levels or mutations of the vitamin D receptor, indicating other factors may influence their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitory effect of 220-oxa-1,25-dihydroxyvitamin D3 on the proliferation of pancreatic cancer cell lines. Kawa, S., Yoshizawa, K., Tokoo, M., et al.[2019]

In a study of 256 chronic pancreatitis patients, only 43% received DEXA bone density testing, with pancreas specialists being the most likely to conduct these tests compared to primary care providers and gastroenterologists.

Vitamin D testing was performed in 82% of patients, with pancreas specialists again showing higher adherence to testing compared to other provider types, highlighting a need for improved preventive care practices among all providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Provider Type Affect Bone Health Surveillance in Chronic Pancreatitis? Srivoleti, P., Yang, AL., Jin, DX., et al.[2021]

In a long-term study of 164 end-stage renal disease patients on hemodialysis, paricalcitol effectively reduced parathyroid hormone (iPTH) levels from a baseline average of 628.3 pg/ml to the target range of 100-300 pg/ml within 5 months, demonstrating its efficacy in managing secondary hyperparathyroidism.

The treatment was well-tolerated, with adverse events occurring in only 26% of patients, primarily involving expected temporary effects like hypercalcemia and hyperphosphatemia, indicating a favorable safety profile for paricalcitol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A long-term, multicenter study of the efficacy and safety of paricalcitol in end-stage renal disease. Lindberg, J., Martin, KJ., González, EA., et al.[2014]

In a clinical trial involving 12 patients with myelodysplastic syndrome (MDS), paricalcitol was well-tolerated, showing minimal side effects, but did not meet efficacy criteria for treatment as a single agent.

While one patient experienced a notable increase in platelet count, the overall results suggest that paricalcitol alone is not effective for MDS, indicating the need for further research into its use in combination with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D(2) analog (Paricalcitol; Zemplar) for treatment of myelodysplastic syndrome. Koeffler, HP., Aslanian, N., O'Kelly, J.[2014]

Paricalcitol, a safe vitamin D analogue, effectively reduces the production of pro-inflammatory cytokines TNF-alpha and IL-8 in vitro, indicating its potential as an immunomodulatory agent.

In a study involving 10 healthy volunteers, paricalcitol was shown to lower elevated cytokine levels caused by lipopolysaccharide (LPS), suggesting it could help manage inflammation in various conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paricalcitol reduces basal and lipopolysaccharide-induced (LPS) TNF-alpha and IL-8 production by human peripheral blood mononuclear cells. Eleftheriadis, T., Antoniadi, G., Liakopoulos, V., et al.[2021]

Patients with chronic pancreatitis (CP) have a significantly higher prevalence of osteoporosis, with about two-thirds affected, primarily due to factors like maldigestion and vitamin D deficiency associated with exocrine pancreatic insufficiency (EPI).

The treatment of osteoporosis in CP should focus on correcting maldigestion through pancreatic enzyme replacement therapy (PERT), which has been shown to improve vitamin D levels and bone density, thereby reducing the risk of fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Pancreatitis and Bone Disease. Barkin, JA., Barkin, JS.[2021]

In a study of 30 patients with chronic pancreatitis and fat malabsorption, daily vitamin D supplementation significantly increased levels of 25-hydroxyvitamin D (25OHD) compared to placebo, demonstrating its efficacy in improving vitamin D status.

Weekly sessions of ultraviolet radiation B (UVB) in a tanning bed did not lead to significant increases in vitamin D levels, indicating that supplementation is a more effective method for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cholecalciferol versus ultraviolet radiation B: effect on vitamin D metabolites in patients with chronic pancreatitis and fat malabsorption - a randomized clinical trial. Bang, UC., Matzen, P., Benfield, T., et al.[2013]

Citations

1. withpower.com withpower.com/trial/paricalcitol-for-chronic-pancreatitis-d74e8

Paricalcitol for Chronic Pancreatitis (ALLIANCE Trial) Paricalcitol has been used safely for years in treating secondary hyperparathyroidism, a condition related to kidney failure, and is generally well ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6049054/

Evidence-based complementary treatment of pancreatic ... 19-nor-1 alpha,25-dihydroxyvitamin D2 (paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivo. Cancer Biol Ther ...

3. cell.com cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00652-9

Mechanism of enhancing chemotherapy efficacy in ... Paricalcitol (P), a vitamin D analog administered with G, reduced stromal activation and tumor size and increased overall survival in orthotopic mouse models of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11009835/

A phase 1 open label, dose escalation study of intravenous ... Paricalcitol can be safely administered in doses up to 7 mcg/kg weekly with fixed-dose rate gemcitabine without dose-limiting hypercalcemia.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024176293

The therapeutic potential of vitamins A, C, and D in ... The aim of this review was to explore the therapeutic potential of complementing standard therapy with natural or synthetic forms of vitamins A, C, and D.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9697664/

19-Nor-1-alpha-25-dihydroxyvitamin D2 (Paricalcitol ... These studies demonstrate that paricalcitol safely and effectively suppresses iPTH levels in hemodialysis patients.

7. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.902639/full

Vitamin D: A Potential Star for Treating Chronic Pancreatitis Vitamin D (VD) and its analogues have been confirmed as pleiotropic regulators of cell proliferation, apoptosis, differentiation and autophagy.

8. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/STUDY00001982

A Pilot Clinical Trial of Paricalcitol for Chronic Pancreatitis The purpose of this study is to examine the feasibility and acceptability of a drug called paricalcitol in adults with chronic pancreatitis (CP).