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Safety Study of Orally Administered Curcuminoids in Adult Subjects With Cystic Fibrosis (SEER)

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
standardized turmeric root extract
Sponsored by
Ramsey, Bonnie, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic Fibrosis, curcuminoids, turmeric root extract, nasal potential difference (NPD), sweat chloride

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female 18 - 40 years of age. Documented history of being homozygous for ΔF508 CFTR genotype. Able to perform spirometry maneuvers, and have a forced expiratory volume at 1 second (FEV1) greater than or equal to 30% of predicted normal for age, gender, and height (Knudson standards) at screening. Oxygen saturation (as measured by pulse oximetry) > 90% on room air at screening. Clinically stable with no evidence of acute upper or lower respiratory tract infection. Non-smoker for at least 6 months prior to screening. Able to understand and sign a written informed consent and comply with the requirements of the study. Exclusion Criteria: Diagnosis of acute pulmonary exacerbation (PE) requiring antibiotic intervention within 4 weeks prior to screening. Patient reported history of viral upper respiratory tract infection within 2 weeks prior to screening. History of major complications of lung disease (including recent massive hemoptysis or pneumothorax) within two months prior to screening Visit. Acute nosebleeds within 14 days prior to screening. Nasal surgery within 4 weeks prior to screening. Begun use of nasal antibiotics, nasal steroids, nasal cromolyn, nasal atrovent, nasal phenylephrine, or oxymetazoline within 14 days prior to screening. Chest x-ray at screening or within 3 months of screening with abnormalities suggesting clinically significant active pulmonary disease other than cystic fibrosis, and/or new CF-specific changes including atelectasis, small pneumothoraces, or pneumonia. EKG at screening which shows clinically significant abnormality including prolonged QTc, bundle branch block, rhythm other than sinus, evidence of ischemic heart disease.

Sites / Locations

  • Johns Hopkins Hospital
  • University of Washington

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

standardized turmeric root extract

Outcomes

Primary Outcome Measures

Safety and tolerability of 14 days of treatment with orally administered curcuminoids as assessed by adverse events, laboratory parameters, and spirometry.

Secondary Outcome Measures

(1) Pharmacokinetics of repeated doses of orally administered curcuminoids. (2) Change in nasal potential difference (NPD) measurements. (3) Change in sweat chloride measurements.

Full Information

First Posted
September 16, 2005
Last Updated
December 18, 2007
Sponsor
Ramsey, Bonnie, MD
Collaborators
Seer Pharmaceuticals, CF Therapeutics Development Network Coordinating Center, Cystic Fibrosis Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00219882
Brief Title
Safety Study of Orally Administered Curcuminoids in Adult Subjects With Cystic Fibrosis
Acronym
SEER
Official Title
A Phase I Safety and Dose Finding Study of Orally Administered Curcuminoids in Adult Subjects With Cystic Fibrosis Who Are Homozygous for Delta F508 Cystic Fibrosis Transmembrane Conductance Regulator (ΔF508 CFTR) Mutation
Study Type
Interventional

2. Study Status

Record Verification Date
December 2007
Overall Recruitment Status
Completed
Study Start Date
April 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
January 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Ramsey, Bonnie, MD
Collaborators
Seer Pharmaceuticals, CF Therapeutics Development Network Coordinating Center, Cystic Fibrosis Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to assess the safety of advancing doses of curcuminoids administered orally for fourteen consecutive days in adult subjects with cystic fibrosis (CF) who are homozygous for ΔF508 CFTR.
Detailed Description
The drug substance being studied is curcumin. Curcumin (diferuloylmethane) is a major constituent in the spice turmeric, which is used as a food worldwide. The pharmacologic rationale for studying curcumin for the treatment of cystic fibrosis is the potential for curcumin to help correct a deficiency of the cystic fibrosis transmembrane regulator (CFTR) protein. Cystic fibrosis results from a mutation of the CFTR gene, which produces abnormal CFTR protein that does properly transport chloride ion and water in the lung leading to abnormal mucus production. Curcumin is a potent inhibitor of the endoplasmic reticulum (ER) Ca2+ pump, and lowers ER calcium concentration. This may allow abnormal CFTR protein to function properly as a chloride channel and correct the cystic fibrosis defect. If this is successful, this effect could be measured as a decrease in the nasal potential difference (NPD) and sweat chloride in cystic fibrosis patients. The primary objective of this study is to assess the safety of advancing doses of curcuminoids administered orally for fourteen consecutive days in adult subjects with cystic fibrosis (CF) who are homozygous for ΔF508 CFTR. The secondary objectives are to obtain pharmacokinetic data for oral curcumoniods in CF subjects and to assess the effectiveness of curcuminoids to alter nasal potential difference (NPD) and seat chloride concentrations.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Cystic Fibrosis, curcuminoids, turmeric root extract, nasal potential difference (NPD), sweat chloride

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
standardized turmeric root extract
Intervention Type
Drug
Intervention Name(s)
standardized turmeric root extract
Other Intervention Name(s)
AFI Curcuminoids
Intervention Description
1.5 gm of standardized tumeric root extract three times per day for seven consecutive days, followed by 3 gm of standardized tumeric root extract three times per day for seven consecutive days
Primary Outcome Measure Information:
Title
Safety and tolerability of 14 days of treatment with orally administered curcuminoids as assessed by adverse events, laboratory parameters, and spirometry.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
(1) Pharmacokinetics of repeated doses of orally administered curcuminoids. (2) Change in nasal potential difference (NPD) measurements. (3) Change in sweat chloride measurements.
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female 18 - 40 years of age. Documented history of being homozygous for ΔF508 CFTR genotype. Able to perform spirometry maneuvers, and have a forced expiratory volume at 1 second (FEV1) greater than or equal to 30% of predicted normal for age, gender, and height (Knudson standards) at screening. Oxygen saturation (as measured by pulse oximetry) > 90% on room air at screening. Clinically stable with no evidence of acute upper or lower respiratory tract infection. Non-smoker for at least 6 months prior to screening. Able to understand and sign a written informed consent and comply with the requirements of the study. Exclusion Criteria: Diagnosis of acute pulmonary exacerbation (PE) requiring antibiotic intervention within 4 weeks prior to screening. Patient reported history of viral upper respiratory tract infection within 2 weeks prior to screening. History of major complications of lung disease (including recent massive hemoptysis or pneumothorax) within two months prior to screening Visit. Acute nosebleeds within 14 days prior to screening. Nasal surgery within 4 weeks prior to screening. Begun use of nasal antibiotics, nasal steroids, nasal cromolyn, nasal atrovent, nasal phenylephrine, or oxymetazoline within 14 days prior to screening. Chest x-ray at screening or within 3 months of screening with abnormalities suggesting clinically significant active pulmonary disease other than cystic fibrosis, and/or new CF-specific changes including atelectasis, small pneumothoraces, or pneumonia. EKG at screening which shows clinically significant abnormality including prolonged QTc, bundle branch block, rhythm other than sinus, evidence of ischemic heart disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chris Goss, MD, MSc
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195-6522
Country
United States

12. IPD Sharing Statement

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Safety Study of Orally Administered Curcuminoids in Adult Subjects With Cystic Fibrosis

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